Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice

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...

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Autores principales:	Ketema Abdissa, Nanthapon Ruangkiattikul, Wiebke Ahrend, Andreas Nerlich, Andreas Beineke, Kristin Laarmann, Nina Janze, Ulrike Lobermeyer, Abdulhadi Suwandi, Christine Falk, Ulrike Schleicher, Christian Bogdan, Siegfried Weiss, Ralph Goethe
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	mycobacterium macrophage inducible or type 2 nitric oxide synthase paratuberculosis johne’s disease Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/195f88f0255048ea8a7eff1678f92304
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spelling	oai:doaj.org-article:195f88f0255048ea8a7eff1678f923042021-11-17T14:21:58ZRelevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice2150-55942150-560810.1080/21505594.2020.1763055https://doaj.org/article/195f88f0255048ea8a7eff1678f923042020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1763055https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Mycobacterium 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.Ketema AbdissaNanthapon RuangkiattikulWiebke AhrendAndreas NerlichAndreas BeinekeKristin LaarmannNina JanzeUlrike LobermeyerAbdulhadi SuwandiChristine FalkUlrike SchleicherChristian BogdanSiegfried WeissRalph GoetheTaylor & Francis Grouparticlemycobacteriummacrophageinducible or type 2 nitric oxide synthaseparatuberculosisjohne’s diseaseInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 465-481 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	mycobacterium macrophage inducible or type 2 nitric oxide synthase paratuberculosis johne’s disease Infectious and parasitic diseases RC109-216
spellingShingle	mycobacterium macrophage inducible or type 2 nitric oxide synthase paratuberculosis johne’s disease Infectious and parasitic diseases RC109-216 Ketema Abdissa Nanthapon Ruangkiattikul Wiebke Ahrend Andreas Nerlich Andreas Beineke Kristin Laarmann Nina Janze Ulrike Lobermeyer Abdulhadi Suwandi Christine Falk Ulrike Schleicher Christian Bogdan Siegfried Weiss Ralph Goethe Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice
description	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.
format	article
author	Ketema Abdissa Nanthapon Ruangkiattikul Wiebke Ahrend Andreas Nerlich Andreas Beineke Kristin Laarmann Nina Janze Ulrike Lobermeyer Abdulhadi Suwandi Christine Falk Ulrike Schleicher Christian Bogdan Siegfried Weiss Ralph Goethe
author_facet	Ketema Abdissa Nanthapon Ruangkiattikul Wiebke Ahrend Andreas Nerlich Andreas Beineke Kristin Laarmann Nina Janze Ulrike Lobermeyer Abdulhadi Suwandi Christine Falk Ulrike Schleicher Christian Bogdan Siegfried Weiss Ralph Goethe
author_sort	Ketema Abdissa
title	Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice
title_short	Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice
title_full	Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice
title_fullStr	Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice
title_full_unstemmed	Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice
title_sort	relevance of inducible nitric oxide synthase for immune control of mycobacterium avium subspecies paratuberculosis infection in mice
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/195f88f0255048ea8a7eff1678f92304
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Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice

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