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Immunopathological mechanisms in the early stage of Mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic emaciating disease of ruminants that causes enormous economic losses to the bovine industry, globally. However, there are still remaining clues to be solved in the pathogenesis and diagnosis of...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934400/ https://www.ncbi.nlm.nih.gov/pubmed/36795721 http://dx.doi.org/10.1371/journal.pone.0281880 |
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author | Lee, Jun Ho Park, Hong-Tae Shim, Soojin Kim, Suji Woo, Sang-Ho Kim, Dae-Yong Yoo, Han Sang |
author_facet | Lee, Jun Ho Park, Hong-Tae Shim, Soojin Kim, Suji Woo, Sang-Ho Kim, Dae-Yong Yoo, Han Sang |
author_sort | Lee, Jun Ho |
collection | PubMed |
description | Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic emaciating disease of ruminants that causes enormous economic losses to the bovine industry, globally. However, there are still remaining clues to be solved in the pathogenesis and diagnosis of the disease. Therefore, an in vivo murine experimental model was tried to understand responses in early stage of MAP infection by oral and intraperitoneal (IP) routes. In the MAP infection size, and weight of spleen and liver were increased in the IP group compared with oral groups. Severe histopathological changes were also observed in the spleen and liver of IP infected mice at 12 weeks post-infection (PI). Acid-fast bacterial burden in the organs was closely related to histopathological lesions. In the cytokine production from splenocytes of MAP-infected mice, higher amounts of in TNF-α, IL-10, and IFN-γ were produced at early stage of IP-infected mice while IL-17 production was different at time and infected groups. This phenomenon may indicate the immune shift from Th1 to Th17 through the time course of MAP infection. Systemic and local responses in the MAP-infection were analyzed by using transcriptomic analysis in the spleens and mesenteric lymph nodes (MLN). Based on the analysis of biological processes at 6 weeks PI in spleen and MLN in each infection group, canonical pathways were analyzed with ingenuity pathway analysis in the immune responses and metabolism especially lipid metabolism. Infected host cells with MAP increased in the production of proinflammatory cytokines and reduced the availability of glucose at early stage of infection (p < 0.05). Also, host cells secreted cholesterol through cholesterol efflux to disturb energy source of MAP. These results reveal immunopathological and metabolic responses in the early stage of MAP infection through the development of a murine model. |
format | Online Article Text |
id | pubmed-9934400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-99344002023-02-17 Immunopathological mechanisms in the early stage of Mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model Lee, Jun Ho Park, Hong-Tae Shim, Soojin Kim, Suji Woo, Sang-Ho Kim, Dae-Yong Yoo, Han Sang PLoS One Research Article Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic emaciating disease of ruminants that causes enormous economic losses to the bovine industry, globally. However, there are still remaining clues to be solved in the pathogenesis and diagnosis of the disease. Therefore, an in vivo murine experimental model was tried to understand responses in early stage of MAP infection by oral and intraperitoneal (IP) routes. In the MAP infection size, and weight of spleen and liver were increased in the IP group compared with oral groups. Severe histopathological changes were also observed in the spleen and liver of IP infected mice at 12 weeks post-infection (PI). Acid-fast bacterial burden in the organs was closely related to histopathological lesions. In the cytokine production from splenocytes of MAP-infected mice, higher amounts of in TNF-α, IL-10, and IFN-γ were produced at early stage of IP-infected mice while IL-17 production was different at time and infected groups. This phenomenon may indicate the immune shift from Th1 to Th17 through the time course of MAP infection. Systemic and local responses in the MAP-infection were analyzed by using transcriptomic analysis in the spleens and mesenteric lymph nodes (MLN). Based on the analysis of biological processes at 6 weeks PI in spleen and MLN in each infection group, canonical pathways were analyzed with ingenuity pathway analysis in the immune responses and metabolism especially lipid metabolism. Infected host cells with MAP increased in the production of proinflammatory cytokines and reduced the availability of glucose at early stage of infection (p < 0.05). Also, host cells secreted cholesterol through cholesterol efflux to disturb energy source of MAP. These results reveal immunopathological and metabolic responses in the early stage of MAP infection through the development of a murine model. Public Library of Science 2023-02-16 /pmc/articles/PMC9934400/ /pubmed/36795721 http://dx.doi.org/10.1371/journal.pone.0281880 Text en © 2023 Lee et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Lee, Jun Ho Park, Hong-Tae Shim, Soojin Kim, Suji Woo, Sang-Ho Kim, Dae-Yong Yoo, Han Sang Immunopathological mechanisms in the early stage of Mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model |
title | Immunopathological mechanisms in the early stage of Mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model |
title_full | Immunopathological mechanisms in the early stage of Mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model |
title_fullStr | Immunopathological mechanisms in the early stage of Mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model |
title_full_unstemmed | Immunopathological mechanisms in the early stage of Mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model |
title_short | Immunopathological mechanisms in the early stage of Mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model |
title_sort | immunopathological mechanisms in the early stage of mycobacterium avium subsp. paratuberculosis infection via different administration routes in a murine model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934400/ https://www.ncbi.nlm.nih.gov/pubmed/36795721 http://dx.doi.org/10.1371/journal.pone.0281880 |
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