Host Transcriptional Profiles and Immunopathologic Response following Mycobacterium avium subsp. paratuberculosis Infection in Mice.

Min-Kyoung Shin,Dae-Yong Kim,Seung Won Shin,Myunghwan Jung,Han Sang Yoo,Hongtae Park,Su-Hyung Lee,Odir A Dellagostin

doi:10.1371/journal.pone.0138770

Abstract

Paratuberculosis or Johne’s disease is a chronic granulomatous enteropathy in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection. In the present study, we examined the host response to MAP infection in spleens of mice in order to investigate the host immunopathology accompanying host-pathogen interaction. Transcriptional profiles of the MAP-infected mice at 3 and 6 weeks p.i. showed severe histopathological changes, whereas those at 12 weeks p.i. displayed reduced lesion severity in the spleen and liver. MAP-infected mice at 3 and 6 weeks p.i. showed up-regulation of interferon-related genes, scavenger receptor, and complement components, suggesting an initial innate immune reaction, such as macrophage activation, bactericidal activity, and macrophage invasion of MAP. Concurrently, MAP-infected mice at 3 and 6 weeks p.i. were also suggested to express M2 macrophage phenotype with up-regulation of Mrc1, and Marco and down-regulation of MHC class II, Ccr7, and Irf5, and canonical pathways related to the T cell response including ICOS-ICOSL signaling in T helper cells, calcium-induced T lymphocyte apoptosis, and CD28 signaling in T helper cell. These results provide information which furthers the understanding of the immunopathologic response to MAP infection in mice, thereby providing insights valuable for research into the pathogenesis for MAP infection.

Highlights

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease, which is characterized by chronic granulomatous enteropathy, persistent diarrhea, progressive wasting, and potential death in ruminants [1,2]
Histopathological changes were observed during the experimental period in spleens and livers of the MAP-infected mice
Moderate effacement of the normal splenic architecture due to infiltration of a moderate number of macrophages with compression to destruction of the splenic white pulp at 6 weeks p.i. and mild infiltration of macrophage in the parafollicular areas.at 12 weeks p.i. were noted in the infected spleen ((Fig 1C(2) and 1C(1))

Summary

Introduction

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease, which is characterized by chronic granulomatous enteropathy, persistent diarrhea, progressive wasting, and potential death in ruminants [1,2]. Paratuberculosis (MAP) is the causative agent of Johne’s disease, which is characterized by chronic granulomatous enteropathy, persistent diarrhea, progressive wasting, and potential death in ruminants [1,2]. Domestic and free-ranging ruminants are the animals primarily vulnerable to MAP, MAP infection has been. A possible link between MAP and Crohn’s disease, which is a type of chronic inflammatory bowel disease in humans, has been mentioned in several studies [6]. Use of ruminants in experimental challenge models for Johne’s disease is complicated by the long experimental period required, wherein the animals have to be maintained until they develop signs of the disease [12,13,14,15]. A bovine model that can be used to study all stages of MAP infection has not been reported to date, a baby goat model has been recently used for studying vaccine strain of MAP [16]

Methods

Results

Conclusion