Loading...
Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice.
Abdissa, Ketema Ruangkiattikul, Nanthapon Ahrend, Wiebke Nerlich, Andreas Beineke, Andreas Laarmann, Kristin Janze, Nina Lobermeyer, Ulrike Suwandi, Abdulhadi Falk, Christine
Abdissa, Ketema
Ruangkiattikul, Nanthapon
Ahrend, Wiebke
Nerlich, Andreas
Beineke, Andreas
Laarmann, Kristin
Janze, Nina
Lobermeyer, Ulrike
Suwandi, Abdulhadi
Falk, Christine
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2020-05-14
Submitted date
Files
Loading...
Open Access article
Adobe PDF, 6.48 MB
Other Titles
Abstract
Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease (JD), an incurable chronic intestinal bowel disease in ruminants. JD occurs worldwide and causes enormous economic burden in dairy industry. Research on JD pathobiology is hampered by its complexity which cannot completely be mimicked by small animal models. As a model the mouse allows dissecting some pathogenicity features of MAP. However, for unknown reasons MAP exhibits reduced growth in granulomas of infected mice compared to other Mycobacterium avium subspecies. Here, we characterized immune reactions of MAP-infected C57BL/6 mice. After infection, mice appeared fully immunocompetent. A strong antigen-specific T cell response was elicited indicated by IFNγ production of splenic T cells re-stimulated with MAP antigens. Function of splenic dendritic cells and proliferation of adoptively transferred antigen-specific CD4+ T cells was unaltered. Isolated splenic myeloid cells from infected mice revealed that MAP resides in CD11b+ macrophages. Importantly, sorted CD11b+CD11c- cells expressed high level of type 2 nitric oxide synthase (NOS2) but only low levels of pro- and anti-inflammatory cytokines. Correspondingly, MAP-infected MAC2 expressing myeloid cells in spleen and liver granuloma displayed strong expression of NOS2. In livers of infected Nos2-/-mice higher bacterial loads, more granuloma and larger areas of tissue damage were observed 5 weeks post infection compared to wild type mice. In vitro, MAP was sensitive to NO released by a NO-donor. Thus, a strong T cell response and concomitant NOS2/NO activity appears to control MAP infection, but allows development of chronicity and pathogen persistence. A similar mechanism might explain persistence of MAP in ruminants.
Citation
Virulence. 2020 Dec;11(1):465-481. doi: 10.1080/21505594.2020.1763055.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
2150-5608
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution 4.0 International