vetpressАграрная наукаAgrarian science0869-81552686-701XРедакция журнала "Аграрная наука"10.32634/0869-8155-2025-399-10-121-132vetpress-3868Research ArticleЗООТЕХНИЯZOOTECHNICSАссоциация полиморфизма rs8193046 гена TLR4 с элементным составом сыворотки крови коров красной степной породыAssociation of the rs8193046 polymorphism of the TLR4 gene with the elemental composition of the blood serum of red steppe cowshttps://orcid.org/0000-0001-6325-7389ТарасоваЕ. И.TarasovaE. I.

Екатерина Ивановна Тарасова - младший научный сотрудник,

ул. 9 Января, 29, Оренбург, 460000

Ekaterina Ivanovna Tarasova - Junior Research Аssistant,

29 9th January Str., Orenburg, 460000

ekaterina45828@mail.ruhttps://orcid.org/0000-0002-5125-5981СизоваЕ. А.SizovaE. A.

Елена Анатольевна Сизова - доктор биологических наук, доцент,

ул. 9 Января, 29, Оренбург, 460000

Elena Anatolyevna Sizova - Doctor of Biological Sciences, Associate Professor,

29 9th January Str., Orenburg, 460000

Sizova.L78@yandex.ruhttps://orcid.org/0000-0002-1589-2211ЯушеваЕ. В.YaushevaE. V.

Елена Владимировна Яушева - кандидат биологических наук,

ул. 9 Января, 29, Оренбург, 460000

Elena Vladimirovna Yausheva - Candidate of Biological Sciences,

29 9th January Str., Orenburg, 460000

vasilena56@mail.ruhttps://orcid.org/0000-0001-9485-7010ЛебедевС. В.LebedevS. V.

Святослав Валерьевич Лебедев - доктор биологических наук, член-корреспондентРоссийской академии наук,

ул. 9 Января, 29, Оренбург, 460000

Svyatoslav Valerievich Lebedev - Doctor of Biological Sciences, Corresponding MemberRussian Academy of Sciences,

29 9th January Str., Orenburg, 460000

lsv74@list.ruФедеральный научный центр биологических систем и агротехнологий Российской академии наукРоссияFederal Research Centre of Biological Systems and Agrotechnologies of the Russian Academy of SciencesRussian Federation202502112025010121132Copyright © Тарасова Е.И., Сизова Е.А., Яушева Е.В., Лебедев С.В., 20252025Тарасова Е.И., Сизова Е.А., Яушева Е.В., Лебедев С.В.Tarasova E.I., Sizova E.A., Yausheva E.V., Lebedev S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vetpress.ru/jour/article/view/3868

В последние годы изучение генетических факторов, влияющих на иммунный ответ, устойчивость к заболеваниям и продуктивность животных, привлекает значительное внимание селекционеров. Одним из таких факторов является толл-подобный рецептор 4 (TLR4), который играет ключевую роль в иммунном ответе. Рецептор реагирует на липополисахаридные компоненты бактериальной клеточной стенки. У крупного рогатого скота идентифицированы 10 функциональных TLR (от TLR1 до TLR10), каждый из которых эволюционировал для распознавания специфических патоген-ассоциированных молекулярных паттернов (PAMP). Генетические полиморфизмы в генах TLR могут влиять на обмен веществ, связанный с усвоением и распределением макро- и микроэлементов, а также определять различия в их содержании в тканях и сыворотке крови.

Цель данного исследования — изучение влияния полиморфизма rs8193046 гена TLR4 на содержание лейкоцитов и элементный состав сыворотки крови коров красной степной породы. Впервые была выявлена связь аллельных вариантов гена TLR4 с содержанием элементов в сыворотке крови и показателями иммунитета у дойных коров этой породы. Генотип GG гена TLR4 был ассоциирован с более высоким содержанием макроэлементов, таких как кальций и фосфор, а также с более низким уровнем токсичных микроэлементов, включая кадмий. Наличие носителей альтернативных аллелей в стаде красной степной породы открывает возможности для селекции, направленной на повышение резистентности к инфекционным заболеваниям.

In recent years, the study of genetic factors affecting the immune response, disease resistance and productivity of animals has attracted considerable attention from breeders. One of these factors is the toll-like receptor 4 (TLR4), which plays a key role in the immune response. The receptor responds to lipopolysaccharide components of the bacterial cell wall. Ten functional TLRs (TLR1 to TLR10) have been identified in cattle, each of which has evolved to recognize specific pathogen-associated molecular patterns (PAMPs). Genetic polymorphisms in TLR genes can affect metabolism associated with the absorption and distribution of macro- and microelements, as well as determine differences in their content in tissues and blood serum.

The purpose of this study is to study the effect of the rs8193046 polymorphism of the TLR4 gene on the content of leukocytes and the elemental composition of the blood serum of cows of the red steppe breed.

For the first time, a connection was found between allelic variants of the TLR4 gene and the content of elements in the blood serum and immunity indices in dairy cows of this breed. The GG genotype of the TLR4 gene was associated with a higher content of macroelements, such as calcium and phosphorus, as well as with a lower level of toxic microelements, including cadmium. The presence of carriers of alternative alleles in the herd of the Red Steppe breed opens up opportunities for selection aimed at increasing resistance to infectious diseases.

TLR4rs8193046элементный составсыворотка кровимолочные коровыкрасный степной скотTLR4rs8193046elemental compositionblood serumdairy cowsred steppe cattleРабота выполнена в соответствии с планом НИР на 2025–2027 гг. Федерального научного центра биологических систем и агротехнологий Российской академии наук (№ FNWZ-2025-0001).The research was carried out in accordance with the research plan for 2025–2027 of the Federal Scientific Center for Biological Systems and Agricultural Technologies of the Russian Academy of Sciences (No. FNWZ-2025-0001).ReferencesMiroshnikov S., Notova S., Kazakova T., Marshinskaia O. The total accumulation of heavy metals in body in connection with the dairy productivity of cows. Environmental Science and Pollution Research International. 2021; 28(36): 49852–49863. https://doi.org/10.1007/s11356-021-14198-6Miroshnikov S., Notova S., Kazakova T., Marshinskaia O. The total accumulation of heavy metals in body in connection with the dairy productivity of cows. Environmental Science and Pollution Research International. 2021; 28(36): 49852–49863. https://doi.org/10.1007/s11356-021-14198-6Горлов И.Ф. и др. Влияние новых кормовых добавок на продуктивность коров красной степной породы. Аграрный вестник Урала. 2023; 04(233): 61‒69. https://doi.org/10.32417/1997-4868-2023-233-04-61-69Gorlov I.F. et al. Influence of feed additives on the productivity of red steppe cows. Agrarian Bulletin of the Urals. 2023; 04(233): 61‒69 (in Russian). https://doi.org/10.32417/1997-4868-2023-233-04-61-69Овчинникова Е.К., Судаков Н.Н., Максимюк Н.Н., Морозов М.В. Совершенствование условий содержания и кормления молочных коров. Аграрная наука. 2024; (12): 70–76. https://doi.org/10.32634/0869-8155-2024-389-12-70-76Ovchinnikova E.K., Sudakov N.N., Maksimyuk N.N., Morozov M.V. Improving the conditions of keeping and feeding dairy cows. Agrarian science. 2024; (12): 70–76 (in Russian). https://doi.org/10.32634/0869-8155-2024-389-12-70-76Rybachuk Zh., Revunets A., Galatyuk O., Romanyshyna T., Behas V. Pharmacological effects of the use of enzyme and probiotic feed additive for dry cows. Наукові горизонти. 2024; 27(6): 9–18. https://doi.org/10.48077/scihor6.2024.09Rybachuk Zh., Revunets A., Galatyuk O., Romanyshyna T., Behas V. Pharmacological effects of the use of enzyme and probiotic feed additive for dry cows. Scientific Horizons. 2024; 27(6): 9–18. https://doi.org/10.48077/scihor6.2024.09Bartens M.-C. et al. Single Nucleotide Polymorphisms in the Bovine TLR2 Extracellular Domain Contribute to Breed and Species-Specific Innate Immune Functionality. Frontiers in Immunology. 2021; 12: 764390. https://doi.org/10.3389/fimmu.2021.764390Bartens M.-C. et al. Single Nucleotide Polymorphisms in the Bovine TLR2 Extracellular Domain Contribute to Breed and Species-Specific Innate Immune Functionality. Frontiers in Immunology. 2021; 12: 764390. https://doi.org/10.3389/fimmu.2021.764390Власенко Н.В., Чанышев М.Д., Хафизов К.Ф., Кузин С.Н., Акимкин В.Г. Значимость генов главного комплекса гистосовместимости в отношении иммунитета против гепатита А. Инфекционные болезни в современном мире: эволюция, текущие и будущие угрозы. Сборник трудов XVI Ежегодного всероссийского конгресса по инфекционным болезням им. академика В.И. Покровского. М.: Медицинское маркетинговое агентство. 2024; 49. https://www.elibrary.ru/athferVlasenko N.V., Chanyshev M.D., Khafizov K.F., Kuzin S.N., Akimkin V.G. The importance of major histocompatibility complex genes in immunity against hepatitis A. Infectious diseases in the modern world: evolution, current and future threats. Proceedings of the XVI Annual All-Russian Congress on Infectious Diseases named after Academician V.I. Pokrovsky. Moscow: Medical Marketing Agency. 2024; 49 (in Russian). https://www.elibrary.ru/athfer.Бородин Н.Е., Сибен А.Н. Генетическое различие в иммунном ответе домашних и диких птиц. Аграрная наука в контексте времени. Сборник трудов LX Международной научно-практической конференция студентов, аспирантов и молодых ученых. Тюмень: Государственный аграрный университет Северного Зауралья. 2025; 5–8. https://www.elibrary.ru/wytryrBorodin N.E., Siben A.N. Genetic differences in the immune response of domestic and wild birds. Agricultural science in the context of time. Proceedings of the LX International scientific and practical conference of students, graduate students and young scientists. Tyumen: State Agrarian University of the Northern TransUrals. 2025; 5–8 (in Russian). https://www.elibrary.ru/wytryrКарпова Н.С., Нурбеков М.К., Дмитренко О.П., Терехина О.Л. Путь от поиска генетической предрасположенности к развитию заболеваний до разработки терапии. От рождения до активного долголетия. Сборник тезисов докладов II Международного форума геномных и биомедицинских технологий. Сургут: Издательский центр Сургутского государственного университета. 2024; 49–50. https://www.elibrary.ru/jlzjwpKarpova N.S., Nurbekov M.K., Dmitrenko O.P., Terekhova O.L. The path from the search for genetic predisposition to disease development to the development of therapy. From birth to active longevity: Collection of abstracts of reports of the II International Forum of Genomic and Biomedical Technologies. Surgut: Publishing Center of Surgut State University. 2024; 49–50 (in Russian). https://www.elibrary.ru/jlzjwpРешетникова А.А. и др. Определение экспрессии генов ТNFAIP3, CDS1 и MTAP в популяции свиней породы крупная белая. Аграрная наука. 2025; (2): 95–100. https://doi.org/10.32634/0869-8155-2025-391-02-95-100Reshetnikova A.A. et al. Determination of TNFAIP3, CDS1 and MTAP gene expression in a population of large white pigs. Agrarian science. 2025; (2): 95–100 (in Russian). https://doi.org/10.32634/0869-8155-2025-391-02-95-100Максимчук М.Г., Левина Г.Н. Молочная продуктивность и функция воспроизводства коров черно-пестрой породы разных генотипов. Аграрная наука. 2023; (8): 53–57. https://doi.org/10.32634/0869-8155-2023-373-8-53-57Maksimchuk M.G., Levina G.N. Milk productivity and reproduction function of black-and-white olland cows of different genotypes. Agrarian science. 2023; (8): 53–57 (in Russian). https://doi.org/10.32634/0869-8155-2023-373-8-53-57Сабетова К.Д. и др. Молочная продуктивность и уровень кетоновых тел в крови коров костромской породы разных генотипов LEP. Аграрная наука. 2024; (6): 56–61. https://doi.org/10.32634/0869-8155-2024-383-6-56-61Sabetova K.D. et al. Milk productivity and the concentration of ketones in the blood of Kostroma cows of different LEP genotypes. Agrarian science. 2024; (6): 56–61 (in Russian). https://doi.org/10.32634/0869-8155-2024-383-6-56-61Тарасова Е.И. Элементный состав сыворотки крови молочных коров с различными полиморфными вариантами гена TLR4. Современные достижения и проблемы физиологии и кормления животных. Сборник тезисов Международного научного форума «Современные достижения и проблемы физиологии и кормления животных», посвященного 120-летию со дня рождения академика А.Д. Синещёкова и 100-летию со дня рождения профессора В.А. Крохиной. Подольск: ФГБНУ ФИЦ ВИЖ им. Л.К. Эрнста, 2024; 62–64. https://www.elibrary.ru/lticzbTarasova E.I. Elemental composition of blood serum of dairy cows with different polymorphic variants of the TLR4 gene. Modern achievements and problems of animal physiology and nutrition: Collection of abstracts of the international scientific forum “Modern achievements and problems of animal physiology and nutrition” dedicated to the 120th anniversary of the birth of academician A.D. Sineshchekov and the 100th anniversary of the birth of professor V.A. Krokhina. Podolsk: L.K. Ernst Federal Research Center for Animal Husbandry. 2024; 62–64 (in Russian). https://www.elibrary.ru/lticzbТарасова Е.И. Полиморфизм гена TLR4 и его влияние на продуктивность и элементный состав крови коров черно-пестрой породы трех областей России. Зоотехния сегодня — приоритеты и перспективы развития. Материалы Международной научнопрактической конференции, посвященной памяти заслуженных деятелей науки Российской Федерации В.И. Левахина и Г.И. Левахина. Оренбург: Федеральный научный центр биологических систем и агротехнологий Российской академии наук. 2025; 151–155. https://www.elibrary.ru/cxmdplTarasova E.I. Polymorphism of the TLR4 gene and its effect on the productivity and elemental composition of the blood of Black-and-White cows in three regions of Russia. Animal science today — priorities and development prospects. Proceedings of the international scientific and practical conference dedicated to the memory of Honored Scientists of the Russian Federation V.I. Levakhin and G.I. Levakhin. Orenburg: Federal Research Center for Biological Systems and Agrotechnologies of the Russian Academy of Sciences. 2025; 151–155 (in Russian). https://www.elibrary.ru/cxmdplChen H. et al. Contribution of the mutation rs8193069 in TLR4 to mastitis resistance and performance in Holstein cows in southern China. Veterinary Medicine and Science. 2022; 8(1): 357–366. https://doi.org/10.1002/vms3.671Chen H. et al. Contribution of the mutation rs8193069 in TLR4 to mastitis resistance and performance in Holstein cows in southern China. Veterinary Medicine and Science. 2022; 8(1): 357–366. https://doi.org/10.1002/vms3.671Zamorano-Algandar R. et al. Genetic Markers Associated with Milk Production and Thermotolerance in Holstein Dairy Cows Managed in a Heat-Stressed Environment. Biology. 2023; 12(5): 679. https://doi.org/10.3390/biology12050679Zamorano-Algandar R. et al. Genetic Markers Associated with Milk Production and Thermotolerance in Holstein Dairy Cows Managed in a Heat-Stressed Environment. Biology. 2023; 12(5): 679. https://doi.org/10.3390/biology12050679Mukherjee S., Huda S., Sinha Babu S.P. Toll-like receptor polymorphism in host immune response to infectious diseases: A review. Scandinavian Journal of Immunology. 2019; 90(1): e12771. https://doi.org/10.1111/sji.12771Mukherjee S., Huda S., Sinha Babu S.P. Toll-like receptor polymorphism in host immune response to infectious diseases: A review. Scandinavian Journal of Immunology. 2019; 90(1): e12771. https://doi.org/10.1111/sji.12771Sameer A.S., Nissar S. Toll-Like Receptors (TLRs): Structure, Functions, Signaling, and Role of Their Polymorphisms in Colorectal Cancer Susceptibility. BioMed Research International. 2021; 2021: 1157023. https://doi.org/10.1155/2021/1157023Sameer A.S., Nissar S. Toll-Like Receptors (TLRs): Structure, Functions, Signaling, and Role of Their Polymorphisms in Colorectal Cancer Susceptibility. BioMed Research International. 2021; 2021: 1157023. https://doi.org/10.1155/2021/1157023Maurić Maljković M., Vlahek I., Piplica A., Ekert Kabalin A., Sušić V., Stevanović V. Prospects of toll-like receptors in dairy cattle breeding. Animal Genetics. 2023; 54(4): 425–434. https://doi.org/10.1111/age.13325Maurić Maljković M., Vlahek I., Piplica A., Ekert Kabalin A., Sušić V., Stevanović V. Prospects of toll-like receptors in dairy cattle breeding. Animal Genetics. 2023; 54(4): 425–434. https://doi.org/10.1111/age.13325Sharma B.S., Leyva I., Schenkel F., Karrow N.A. Association of Toll-Like Receptor 4 Polymorphisms with Somatic Cell Score and Lactation Persistency in Holstein Bulls. Journal of Dairy Science. 2006; 89(9): 3626–3635. https://doi.org/10.3168/jds.S0022-0302(06)72402-XSharma B.S., Leyva I., Schenkel F., Karrow N.A. Association of Toll-Like Receptor 4 Polymorphisms with Somatic Cell Score and Lactation Persistency in Holstein Bulls. Journal of Dairy Science. 2006; 89(9): 3626–3635. https://doi.org/10.3168/jds.S0022-0302(06)72402-XWang M. et al. Toll-like receptor 4 gene polymorphisms influence milk production traits in Chinese Holstein cows. Journal of Dairy Research. 2018; 85(4): 407–411. https://doi.org/10.1017/S0022029918000535Wang M. et al. Toll-like receptor 4 gene polymorphisms influence milk production traits in Chinese Holstein cows. Journal of Dairy Research. 2018; 85(4): 407–411. https://doi.org/10.1017/S0022029918000535Gopi B. et al. Single-nucleotide polymorphisms in CLEC7A, CD209 and TLR4 gene and their association with susceptibility to paratuberculosis in Indian cattle. Journal of Genetics. 2020; 99: 14. https://doi.org/10.1007/s12041-019-1172-4Gopi B. et al. Single-nucleotide polymorphisms in CLEC7A, CD209 and TLR4 gene and their association with susceptibility to paratuberculosis in Indian cattle. Journal of Genetics. 2020; 99: 14. https://doi.org/10.1007/s12041-019-1172-4Badami S., Thanislass J., Barathiraja S., Anitha T., Upadhyaya I., Kumar Mukhopadhyay H. Identification of single nucleotide variations in the Toll-like receptor 9 (TLR9) gene and its association to mastitis susceptibility in dairy cattle. Biological Rhythm Research. 2019; 50(6): 887–896. https://doi.org/10.1080/09291016.2018.1502233Badami S., Thanislass J., Barathiraja S., Anitha T., Upadhyaya I., Kumar Mukhopadhyay H. Identification of single nucleotide variations in the Toll-like receptor 9 (TLR9) gene and its association to mastitis susceptibility in dairy cattle. Biological Rhythm Research. 2019; 50(6): 887–896. https://doi.org/10.1080/09291016.2018.1502233Свириденко Г.М., Мордвинова В.А., Вахрушева Д.С., Остроухова И.Л. Маститы — проблема безопасности, качества и сыропригодности молока сырого. Сыроделие и маслоделие. 2024; (3): 58–63. https://doi.org/10.21603/2073-4018-2024-3-5Sviridenko G.M., Mordvinova V.A., Vakhrusheva D.S., Ostroukhova I.L. Mastitis — a problem of safety, quality and suitability of raw milk for cheese production. Syrodeliye i maslodeliye (Cheese and butter making). 2024; (3): 58–63 (in Russian). https://doi.org/10.21603/2073-4018-2024-3-5Tarasova E., Notova S., Markova I., Kataev V., Plotnikov A. PSI-B-27 Association of multiple SNP in the LRP4 gene with features of the cattle elemental status. Journal of Animal Science. 2021; 99(S3): 227. https://doi.org/10.1093/jas/skab235.414Tarasova E., Notova S., Markova I., Kataev V., Plotnikov A. PSI-B-27 Association of multiple SNP in the LRP4 gene with features of the cattle elemental status. Journal of Animal Science. 2021; 99(S3): 227. https://doi.org/10.1093/jas/skab235.414Sizova E.A. et al. Serum and Hair Trace Element and Mineral Levels in Dairy Cows in Relation to Daily Milk Yield. Biological Trace Element Research. 2022; 200(6): 2709–2715. https://doi.org/10.1007/s12011-021-02878-wSizova E.A. et al. Serum and Hair Trace Element and Mineral Levels in Dairy Cows in Relation to Daily Milk Yield. Biological Trace Element Research. 2022; 200(6): 2709–2715. https://doi.org/10.1007/s12011-021-02878-wMiroshnikov S.A., Skalny A.V., Zavyalov O.A., Frolov A.N., Grabeklis A.R. The Reference Values of Hair Content of Trace Elements in Dairy Cows of Holstein Breed. Biological Trace Element Research. 2020; 194(1): 145–151. https://doi.org/10.1007/s12011-019-01768-6Miroshnikov S.A., Skalny A.V., Zavyalov O.A., Frolov A.N., Grabeklis A.R. The Reference Values of Hair Content of Trace Elements in Dairy Cows of Holstein Breed. Biological Trace Element Research. 2020; 194(1): 145–151. https://doi.org/10.1007/s12011-019-01768-6Littledike E.T., Wittum T.E., Jenkins T.G. Effect of breed, intake, and carcass composition on the status of several macro and trace minerals of adult beef cattle. Journal of Animal Science. 1995; 73(7): 2113–2119. https://doi.org/10.2527/1995.7372113xLittledike E.T., Wittum T.E., Jenkins T.G. Effect of breed, intake, and carcass composition on the status of several macro and trace minerals of adult beef cattle. Journal of Animal Science. 1995; 73(7): 2113–2119. https://doi.org/10.2527/1995.7372113xElmaghraby M.M., El-Nahas A.F., Fathala M.M., Sahwan F.M., Tag El-Dien M.A. Association of toll-like receptors 2 and 6 polymorphism with clinical mastitis and production traits in Holstein cattle. Iranian Journal of Veterinary Research. 2018; 19(3): 202–207.Elmaghraby M.M., El-Nahas A.F., Fathala M.M., Sahwan F.M., Tag El-Dien M.A. Association of toll-like receptors 2 and 6 polymorphism with clinical mastitis and production traits in Holstein cattle. Iranian Journal of Veterinary Research. 2018; 19(3): 202–207.Sharma B.S. et al. Association of TLR4 polymorphisms with Mycobacterium avium subspecies paratuberculosis infection status in Canadian Holsteins. Animal Genetics. 2015; 46(5): 560–565. https://doi.org/10.1111/age.12333Sharma B.S. et al. Association of TLR4 polymorphisms with Mycobacterium avium subspecies paratuberculosis infection status in Canadian Holsteins. Animal Genetics. 2015; 46(5): 560–565. https://doi.org/10.1111/age.12333El-Zayat S.R., Sibaii H., Mannaa F.A. Micronutrients and many important factors that affect the physiological functions of toll-like receptors. Bulletin of the National Research Centre. 2019; 43: 123. https://doi.org/10.1186/s42269-019-0165-zEl-Zayat S.R., Sibaii H., Mannaa F.A. Micronutrients and many important factors that affect the physiological functions of toll-like receptors. Bulletin of the National Research Centre. 2019; 43: 123. https://doi.org/10.1186/s42269-019-0165-zYang J. et al. Regularity of Toll-Like Receptors in Bovine Mammary Epithelial Cells Induced by Mycoplasma bovis. Frontiers in Veterinary Science. 2022; 9: 846700. https://doi.org/10.3389/fvets.2022.846700Yang J. et al. Regularity of Toll-Like Receptors in Bovine Mammary Epithelial Cells Induced by Mycoplasma bovis. Frontiers in Veterinary Science. 2022; 9: 846700. https://doi.org/10.3389/fvets.2022.846700Zhou H., Cheng L., Gong H., Byun S.O., Edwards G.R., Hickford J.G.H. Variation in the Toll-like Receptor 4 (TLR4) gene affects milk traits in dairy cows. Journal of Dairy Research. 2017; 84(4): 426–429. https://doi.org/10.1017/S0022029917000711Zhou H., Cheng L., Gong H., Byun S.O., Edwards G.R., Hickford J.G.H. Variation in the Toll-like Receptor 4 (TLR4) gene affects milk traits in dairy cows. Journal of Dairy Research. 2017; 84(4): 426–429. https://doi.org/10.1017/S0022029917000711Spears J.W. Micronutrients and immune function in cattle. Proceedings of the Nutrition Society. 2000; 59(4): 587–594. https://doi.org/10.1017/S0029665100000835Spears J.W. Micronutrients and immune function in cattle. Proceedings of the Nutrition Society. 2000; 59(4): 587–594. https://doi.org/10.1017/S0029665100000835Arthington J.D., Ranches J. Trace Mineral Nutrition of Grazing Beef Cattle. Animals. 2021; 11(10): 2767. https://doi.org/10.3390/ani11102767Arthington J.D., Ranches J. Trace Mineral Nutrition of Grazing Beef Cattle. Animals. 2021; 11(10): 2767. https://doi.org/10.3390/ani11102767Луцай В.И., Руденко П.А., Сибирцев В.Д., Нефедов А.М. Эффективность терапии высокопродуктивных коров при коморбидном течении акушерско-гинекологической и ортопедической патологии. Аграрная наука. 2025; (5): 41–47. https://doi.org/10.32634/0869-8155-2025-394-05-41-47Lutsaу V.I., Rudenko P.A., Sibirtsev V.D., Nefedov A.M. Efficiency of therapy of highly productive cows with comorbid obstetricgynecological and orthopedic pathology. Agrarian science. 2025; (5): 41–47 (in Russian). https://doi.org/10.32634/0869-8155-2025-394-05-41-47Spears J.W., Weiss W.P. Invited Review: Mineral and vitamin nutrition in ruminants. The Professional Animal Scientist. 2014; 30(2): 180–191. https://doi.org/10.15232/S1080-7446(15)30103-0Spears J.W., Weiss W.P. Invited Review: Mineral and vitamin nutrition in ruminants. The Professional Animal Scientist. 2014; 30(2): 180–191. https://doi.org/10.15232/S1080-7446(15)30103-0Munteanu C., Schwartz B. The relationship between nutrition and the immune system. Frontiers in Nutrition. 2022; 9: 1082500. https://doi.org/10.3389/fnut.2022.1082500Munteanu C., Schwartz B. The relationship between nutrition and the immune system. Frontiers in Nutrition. 2022; 9: 1082500. https://doi.org/10.3389/fnut.2022.1082500Zhu C., Chen G., Yao J., Lin W. Effect of infection after liver cancer interventional therapy on T lymphocyte subsets and Toll-like receptors in peripheral blood mononuclear cells and its mechanism. Advances in Clinical and Experimental Medicine. 2022; 31(1): 17–23. https://doi.org/10.17219/acem/141499Zhu C., Chen G., Yao J., Lin W. Effect of infection after liver cancer interventional therapy on T lymphocyte subsets and Toll-like receptors in peripheral blood mononuclear cells and its mechanism. Advances in Clinical and Experimental Medicine. 2022; 31(1): 17–23. https://doi.org/10.17219/acem/141499Ribeiro-Gomes F.L. et al. Neutrophils Activate Macrophages for Intracellular Killing of Leishmania major through Recruitment of TLR4 by Neutrophil Elastase. Journal of Immunology. 2007; 179(6): 3988–3994. https://doi.org/10.4049/jimmunol.179.6.3988Ribeiro-Gomes F.L. et al. Neutrophils Activate Macrophages for Intracellular Killing of Leishmania major through Recruitment of TLR4 by Neutrophil Elastase. Journal of Immunology. 2007; 179(6): 3988–3994. https://doi.org/10.4049/jimmunol.179.6.3988Puck A. et al. The soluble cytoplasmic tail of CD45 regulates T-cell activation via TLR4 signaling. European Journal of Immunology. 2021; 51(12): 3176–3185. https://doi.org/10.1002/eji.202149227Puck A. et al. The soluble cytoplasmic tail of CD45 regulates T-cell activation via TLR4 signaling. European Journal of Immunology. 2021; 51(12): 3176–3185. https://doi.org/10.1002/eji.202149227Mitsuhashi M. Ex vivo simulation of leukocyte function: Stimulation of specific subsets of leukocytes in whole blood followed by the measurement of function-associated mRNAs. Journal of Immunological Methods. 2010; 363(1): 95–100. https://doi.org/10.1016/j.jim.2010.10.002Mitsuhashi M. Ex vivo simulation of leukocyte function: Stimulation of specific subsets of leukocytes in whole blood followed by the measurement of function-associated mRNAs. Journal of Immunological Methods. 2010; 363(1): 95–100. https://doi.org/10.1016/j.jim.2010.10.002Sanguinetti C. et al. Binding of Gamma-Glutamyl Transferase to TLR4 Signalling Allows Tissue Factor Activation in Monocytes. International Journal of Molecular Sciences. 2022; 23(20): 12207. https://doi.org/10.3390/ijms232012207Sanguinetti C. et al. Binding of Gamma-Glutamyl Transferase to TLR4 Signalling Allows Tissue Factor Activation in Monocytes. International Journal of Molecular Sciences. 2022; 23(20): 12207. https://doi.org/10.3390/ijms232012207Lu P. et al. Intestinal epithelial Toll-like receptor 4 prevents metabolic syndrome by regulating interactions between microbes and intestinal epithelial cells in mice. Mucosal Immunology. 2018; 11(3): 727–740. https://doi.org/10.1038/mi.2017.114Lu P. et al. Intestinal epithelial Toll-like receptor 4 prevents metabolic syndrome by regulating interactions between microbes and intestinal epithelial cells in mice. Mucosal Immunology. 2018; 11(3): 727–740. https://doi.org/10.1038/mi.2017.114Wathes D.C. et al. Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation. Journal of Dairy Science. 2021; 104(3): 3596–3616. https://doi.org/10.3168/jds.2020-19165Wathes D.C. et al. Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation. Journal of Dairy Science. 2021; 104(3): 3596–3616. https://doi.org/10.3168/jds.2020-19165Kenny E.F., Quinn S.R., Doyle S.L., Vink P.M., van Eenennaam H., O’Neill L.A.J. Bruton’s Tyrosine Kinase Mediates the Synergistic Signalling between TLR9 and the B Cell Receptor by Regulating Calcium and Calmodulin. PloS ONE. 2013; 8(8): e74103. https://doi.org/10.1371/journal.pone.0074103Kenny E.F., Quinn S.R., Doyle S.L., Vink P.M., van Eenennaam H., O’Neill L.A.J. Bruton’s Tyrosine Kinase Mediates the Synergistic Signalling between TLR9 and the B Cell Receptor by Regulating Calcium and Calmodulin. PloS ONE. 2013; 8(8): e74103. https://doi.org/10.1371/journal.pone.0074103Shintani Y. et al. Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2. EMBO Reports. 2014; 15(4): 438–445. https://doi.org/10.1002/embr.201337945Shintani Y. et al. Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2. EMBO Reports. 2014; 15(4): 438–445. https://doi.org/10.1002/embr.201337945Tang S. et al. Extracellular calcium elicits feedforward regulation of the Toll-like receptor-triggered innate immune response. Cellular & Molecular Immunology. 2017; 14(2): 180–191. https://doi.org/10.1038/cmi.2015.59Tang S. et al. Extracellular calcium elicits feedforward regulation of the Toll-like receptor-triggered innate immune response. Cellular & Molecular Immunology. 2017; 14(2): 180–191. https://doi.org/10.1038/cmi.2015.59Oh-hora M. et al. Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nature Immunology. 2008; 9(4): 432–443. https://doi.org/10.1038/ni1574Oh-hora M. et al. Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nature Immunology. 2008; 9(4): 432–443. https://doi.org/10.1038/ni1574Hogan P.G., Lewis R.S., Rao A. Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI. Annual Review of Immunology. 2010; 28: 491–533. https://doi.org/10.1146/annurev.immunol.021908.132550Hogan P.G., Lewis R.S., Rao A. Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI. Annual Review of Immunology. 2010; 28: 491–533. https://doi.org/10.1146/annurev.immunol.021908.132550Moreira V.R., Zeringue L.K., Williams C.C., Leonardi C., McCormick M.E. Influence of calcium and phosphorus feeding on markers of bone metabolism in transition cows. Journal of Dairy Science. 2009; 92(10): 5189–5198. https://doi.org/10.3168/jds.2009-2289Moreira V.R., Zeringue L.K., Williams C.C., Leonardi C., McCormick M.E. Influence of calcium and phosphorus feeding on markers of bone metabolism in transition cows. Journal of Dairy Science. 2009; 92(10): 5189–5198. https://doi.org/10.3168/jds.2009-2289Wächter S., Cohrs I., Golbeck L., Wilkens M.R., Grünberg W. Effects of restricted dietary phosphorus supply to dry cows on periparturient calcium status. Journal of Dairy Science. 2022; 105(1): 748‒760. https://doi.org/10.3168/jds.2021-20726Wächter S., Cohrs I., Golbeck L., Wilkens M.R., Grünberg W. Effects of restricted dietary phosphorus supply to dry cows on periparturient calcium status. Journal of Dairy Science. 2022; 105(1): 748‒760. https://doi.org/10.3168/jds.2021-20726Zhang D. et al. High Phosphate-Induced Calcification of Vascular Smooth Muscle Cells is Associated with the TLR4/NF-κb Signaling Pathway. Kidney and Blood Pressure Research. 2018; 42(6): 1205–1215. https://doi.org/10.1159/000485874Zhang D. et al. High Phosphate-Induced Calcification of Vascular Smooth Muscle Cells is Associated with the TLR4/NF-κb Signaling Pathway. Kidney and Blood Pressure Research. 2018; 42(6): 1205–1215. https://doi.org/10.1159/000485874Almousa L.A., Salter A.M., Langley-Evans S.C. Varying magnesium concentration elicits changes in inflammatory response in human umbilical vein endothelial cells (HUVECs). Magnesium Research. 2018; 31(3): 99–109. https://doi.org/10.1684/mrh.2018.0439Almousa L.A., Salter A.M., Langley-Evans S.C. Varying magnesium concentration elicits changes in inflammatory response in human umbilical vein endothelial cells (HUVECs). Magnesium Research. 2018; 31(3): 99–109. https://doi.org/10.1684/mrh.2018.0439Haase H. et al. Zinc Signals Are Essential for Lipopolysaccharide-Induced Signal Transduction in Monocytes. Journal of Immunology. 2008; 181(9): 6491–6502. https://doi.org/10.4049/jimmunol.181.9.6491Haase H. et al. Zinc Signals Are Essential for LipopolysaccharideInduced Signal Transduction in Monocytes. Journal of Immunology. 2008; 181(9): 6491–6502. https://doi.org/10.4049/jimmunol.181.9.6491Скальный А.В., Сотникова Т.И., Коробейникова Т.В., Тиньков А.А. Значение коррекции дефицита цинка в практической медицине: обзор. Сеченовский вестник. 2022; 13(4): 4–17. https://doi.org/10.47093/22187332.2022.13.4.4-17Skalny A.V., Sotnikova T.I., Korobeynikova T.V., Tinkov A.A. Significance of zinc deficiency correction for practical medicine: a review. Sechenov Medical Journal. 2022; 13(4): 4–17 (in Russian). https://doi.org/10.47093/2218-7332.2022.13.4.4-17Liu X. et al. Zinc finger protein ZBTB20 promotes toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription. Proceedings of the National Academy of Sciences. 2013; 110(27): 11097–11102. https://doi.org/10.1073/pnas.1301257110Liu X. et al. Zinc finger protein ZBTB20 promotes toll-like receptor-triggered innate immune responses by repressing IκBα gene transcription. Proceedings of the National Academy of Sciences. 2013; 110(27): 11097–11102. https://doi.org/10.1073/pnas.1301257110Sharif-Askari E. et al. Zinc Finger Protein Gfi1 Controls the Endotoxin-Mediated Toll-Like Receptor Inflammatory Response by Antagonizing NF-κB p65. Molecular and Cellular Biology. 2010; 30(16): 3929–3942. https://doi.org/10.1128/MCB.00087-10Sharif-Askari E. et al. Zinc Finger Protein Gfi1 Controls the Endotoxin-Mediated Toll-Like Receptor Inflammatory Response by Antagonizing NF-κB p65. Molecular and Cellular Biology. 2010; 30(16): 3929–3942. https://doi.org/10.1128/MCB.00087-10Maiguma M. et al. Dietary Zinc Is a Key Environmental Modifier in the Progression of IgA Nephropathy. PLoS ONE. 2014; 9(2): e90558. https://doi.org/10.1371/journal.pone.0090558Maiguma M. et al. Dietary Zinc Is a Key Environmental Modifier in the Progression of IgA Nephropathy. PLoS ONE. 2014; 9(2): e90558. https://doi.org/10.1371/journal.pone.0090558Kamei N. et al. Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance. Journal of Biological Chemistry. 2006; 281(36): 26602–26614. https://doi.org/10.1074/jbc.M601284200Kamei N. et al. Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance. Journal of Biological Chemistry. 2006; 281(36): 26602–26614. https://doi.org/10.1074/jbc.M601284200de Pontual L. Iron and susceptibility to infections. Archives de Pédiatrie. 2017; 24(5S): 5S14–5S17 (in French). https://doi.org/10.1016/S0929-693X(17)24004-4de Pontual L. Iron and susceptibility to infections. Archives de Pédiatrie. 2017; 24(5S): 5S14–5S17 (in French). https://doi.org/10.1016/S0929-693X(17)24004-4Balounová J., Vavrochová T., Benešová M., Ballek O., Kolář M., Filipp D. Toll-like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis. European Journal of Immunology. 2014; 44(5): 1491–1502. https://doi.org/10.1002/eji.201344040Balounová J., Vavrochová T., Benešová M., Ballek O., Kolář M., Filipp D. Toll-like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis. European Journal of Immunology. 2014; 44(5): 1491–1502. https://doi.org/10.1002/eji.201344040

The authors declare that there are no conflicts of interest present.