Phenotypes of macrophages present in the intestine are impacted by stage of disease in cattle naturally infected with Mycobacterium avium subsp. paratuberculosis

Authors

Caitlin J. Jenvey, USDA-ARS, National Animal Disease Center
Adrienne L. Shircliff, USDA-ARS, National Animal Disease CenterFollow
J. P. Bannantine, USDA-ARS, National Animal Disease CenterFollow
Judith R. Stabel, USDA-ARS, National Animal Disease CenterFollow

Date of this Version

2019

Citation

Jenvey CJ, Shircliff AL, Bannantine JP, Stabel JR (2019) Phenotypes of macrophages present in the intestine are impacted by stage of disease in cattle naturally infected with Mycobacterium avium subsp. paratuberculosis. PLoS ONE 14(5): e0217649. https://doi.org/ 10.1371/journal.pone.0217649

Comments

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Abstract

Macrophages play an important role in the host immune response to Mycobacterium avium subsp. paratuberculosis (MAP) infection, however, MAP is able to disrupt normal macro- phage functions to avoid destruction. It is unclear whether the phenotypes of macrophages present in the target tissue play a role in the inability to clear MAP infection. The aim of this study was to identify macrophage phenotypes (host defense or resolution and repair) present within the bovine ileum of naturally infected cattle, as well as to ascertain abundance of each macrophage phenotype present during different stages of MAP infection. Immunofluo- rescent (IF) labeling was performed on frozen bovine mid-ileal tissue sections collected from 28 Holstein dairy cows. Comprehensive IF staining for cytokines, such as IFN-γ, IL- 1Ra, IL-1β, IL-10, TGF-β, TNF-α, and uNOS, along with markers such as CD163, CD206, and TLR4, served to define the macrophage phenotypes. Overall, cows in the clinical stage of disease demonstrated significantly higher numbers of resolution and repair macrophages and lower numbers of host defense macrophages in the ileal tissue. Interestingly, subclinically affected cows with asymptomatic disease had a nearly equal ratio of host defense and resolution and repair macrophage phenotypes, whereas macrophage phenotype was skewed to a host defense macrophage in the tissues of the control noninfected cows. The preponderance of M2-like resolution and repair phenotype for macrophages in the tissues of cows with clinical disease would explain why the host fails to control and/or clear the infection, leading to a higher MAP burden. The results of the current study offer insight into the disparate macrophage phenotypes present in the bovine ileum during different stages of infection.