Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.

Progress in tuberculosis vaccine development is hampered by an incomplete understanding of the immune mechanisms that protect against infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Although the M72/ASOE1 trial yielded encouraging results (54% efficacy in subjec...

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Autores principales:	Johannes Nemeth, Gregory S Olson, Alissa C Rothchild, Ana N Jahn, Dat Mai, Fergal J Duffy, Jared L Delahaye, Sanjay Srivatsan, Courtney R Plumlee, Kevin B Urdahl, Elizabeth S Gold, Alan Aderem, Alan H Diercks
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8b125e515468469890da614482c96ca1
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spelling	oai:doaj.org-article:8b125e515468469890da614482c96ca12021-12-02T20:00:18ZContained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.1553-73661553-737410.1371/journal.ppat.1008655https://doaj.org/article/8b125e515468469890da614482c96ca12020-07-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1008655https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Progress in tuberculosis vaccine development is hampered by an incomplete understanding of the immune mechanisms that protect against infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Although the M72/ASOE1 trial yielded encouraging results (54% efficacy in subjects with prior exposure to Mtb), a highly effective vaccine against adult tuberculosis remains elusive. We show that in a mouse model, establishment of a contained and persistent yet non-pathogenic infection with Mtb ("contained Mtb infection", CMTB) rapidly and durably reduces tuberculosis disease burden after re-exposure through aerosol challenge. Protection is associated with elevated activation of alveolar macrophages, the first cells that respond to inhaled Mtb, and accelerated recruitment of Mtb-specific T cells to the lung parenchyma. Systems approaches, as well as ex vivo functional assays and in vivo infection experiments, demonstrate that CMTB reconfigures tissue resident alveolar macrophages via low grade interferon-γ exposure. These studies demonstrate that under certain circumstances, the continuous interaction of the immune system with Mtb is beneficial to the host by maintaining elevated innate immune responses.Johannes NemethGregory S OlsonAlissa C RothchildAna N JahnDat MaiFergal J DuffyJared L DelahayeSanjay SrivatsanCourtney R PlumleeKevin B UrdahlElizabeth S GoldAlan AderemAlan H DiercksPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 16, Iss 7, p e1008655 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Johannes Nemeth Gregory S Olson Alissa C Rothchild Ana N Jahn Dat Mai Fergal J Duffy Jared L Delahaye Sanjay Srivatsan Courtney R Plumlee Kevin B Urdahl Elizabeth S Gold Alan Aderem Alan H Diercks Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.
description	Progress in tuberculosis vaccine development is hampered by an incomplete understanding of the immune mechanisms that protect against infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Although the M72/ASOE1 trial yielded encouraging results (54% efficacy in subjects with prior exposure to Mtb), a highly effective vaccine against adult tuberculosis remains elusive. We show that in a mouse model, establishment of a contained and persistent yet non-pathogenic infection with Mtb ("contained Mtb infection", CMTB) rapidly and durably reduces tuberculosis disease burden after re-exposure through aerosol challenge. Protection is associated with elevated activation of alveolar macrophages, the first cells that respond to inhaled Mtb, and accelerated recruitment of Mtb-specific T cells to the lung parenchyma. Systems approaches, as well as ex vivo functional assays and in vivo infection experiments, demonstrate that CMTB reconfigures tissue resident alveolar macrophages via low grade interferon-γ exposure. These studies demonstrate that under certain circumstances, the continuous interaction of the immune system with Mtb is beneficial to the host by maintaining elevated innate immune responses.
format	article
author	Johannes Nemeth Gregory S Olson Alissa C Rothchild Ana N Jahn Dat Mai Fergal J Duffy Jared L Delahaye Sanjay Srivatsan Courtney R Plumlee Kevin B Urdahl Elizabeth S Gold Alan Aderem Alan H Diercks
author_facet	Johannes Nemeth Gregory S Olson Alissa C Rothchild Ana N Jahn Dat Mai Fergal J Duffy Jared L Delahaye Sanjay Srivatsan Courtney R Plumlee Kevin B Urdahl Elizabeth S Gold Alan Aderem Alan H Diercks
author_sort	Johannes Nemeth
title	Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.
title_short	Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.
title_full	Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.
title_fullStr	Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.
title_full_unstemmed	Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.
title_sort	contained mycobacterium tuberculosis infection induces concomitant and heterologous protection.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/8b125e515468469890da614482c96ca1
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Contained Mycobacterium tuberculosis infection induces concomitant and heterologous protection.

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