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- Title
L’inibizione di mTOR nei macrofagi bovini derivati dai monociti e nelle cellule dendritiche rappresenta una potenziale causa di disfunzione immunitaria nelle vacche da latte durante il post partum.
- Authors
Sipka, Anja S.; Chandler, Tawny L.; Weichhart, Thomas; Schuberth, Hans-Joachim; Mann, Sabine
- Abstract
Dairy cattle experience a profound nutrient defi cit postpartum that is associated with immune dysfunction characterized by heightened infl ammation and reduced pathogen clearance. The activation of the central nutrient-sensing mTOR pathway is comparatively reduced in leukocytes of early postpartum dairy cows during this time of most pronounced nutrient defi cit. We assessed the effect of pharmacological mTOR inhibition (Torin?1, rapamycin) on differentiation of monocyte derived classically (M1) and alternatively (M2) activated macrophages (MPh) and dendritic cells (moDC) from 12 adult dairy cows. Treatment with mTOR inhibitors generated M1 MPh with increased oxidative burst and expression of IL12 subunits but decreased phagocytosis and expression of IL1B, IL6, and IL10. In M2 MPh, treatment inhibited expression of regulatory features (CD163, ARG2, IL10) skewing the cells toward an M1-like phenotype. In moDC, mTOR inhibition increased expression of pro-infl ammatory cytokines (IL12A, IL12B, IL1B, IL6) and surface CD80. In co-culture with mixed lymphocytes, mTOR-inhibited moDC exhibited a cytokine profi le favoring a Th1 response with increased TNF and IFNG production and decreased IL10 concentrations. We conclude that mTOR inhibition in vitro promoted differentiation of infl ammatory macrophages with reduced regulatory features and generation of Th1-favoring dendritic cells. These mechanisms could contribute to immune dysregulation in postpartum dairy cows.
- Publication
Summa, Animali da Reddito, 2023, Vol 18, Issue 1, p29
- ISSN
1828-5546
- Publication type
Article