Stage of infection with Mycobacterium avium subsp. paratuberculosis impacts expression of Rab5, Rab7, and CYP27B1 in macrophages within the ileum of naturally infected cows

Frontiers in Veterinary Science

Veterinary Science

Mark Heggen¹  Shankumar Mooyottu²  Taylor L. T. Wherry³  Adrienne L. Shircliff⁴  Judith R. Stabel⁴ 

[1] Department of Nutritional Sciences, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, WI, United States;Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, United States;Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA, United States;United States Department of Agriculture-Agricultural Research Service (USDA-ARS), National Animal Disease Center, Ames, IA, United States;United States Department of Agriculture-Agricultural Research Service (USDA-ARS), National Animal Disease Center, Ames, IA, United States;

关键词: Mycobacterium avium;    macrophage;    Rab5;    Rab7;    vitamin D;    CYP27B1;    CYP24A1;    bovine;   

DOI  :  10.3389/fvets.2023.1117591

 received in 2022-12-06, accepted in 2023-01-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionMacrophages are the preferential target of Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of ruminant paratuberculosis. Uptake of pathogens by intestinal macrophages results in their trafficking through endosomal compartments, ultimately leading to fusion with an acidic lysosome to destroy the pathogen. MAP possesses virulence factors which disrupt these endosomal pathways. Additionally, levels of serum vitamin D3 have proven relevant to host immunity. Dynamics of endosomal trafficking and vitamin D3 metabolism have been largely unexplored in bovine paratuberculosis.MethodsThis study aimed to characterize expression of early and late endosomal markers Rab5 and Rab7, respectively, within CD68+ macrophages in frozen mid-ileum sections harvested from cows at different stages of natural paratuberculosis infection. Additionally, factors of vitamin D3 signaling and metabolism were characterized through expression of vitamin D3 activating enzyme 1α-hydroxylase (CYP27B1), vitamin D3 inactivating enzyme 24-hydroxylase (CYP24A1), and vitamin D3 receptor (VDR) within CD68+ ileal macrophages.Results and discussionCows with clinical paratuberculosis had significantly greater macrophage and MAP burden overall, as well as intracellular MAP. Total expression of Rab5 within macrophages was reduced in clinical cows; however, Rab5 and MAP colocalization was significantly greater in this group. Intracellular Rab7 colocalization with MAP was not detected in subclinical or Johne's Disease negative (JD-) control cows but was present in clinical cows. Additionally, macrophage CYP27B1 expression was significantly reduced in clinical cows. Taken together, the results from this study show disparate patterns of expression for key mediators in intracellular MAP trafficking and vitamin D metabolism for cows at different stages of paratuberculosis.

【 授权许可】

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Copyright © 2023 Wherry, Heggen, Shircliff, Mooyottu and Stabel.