Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.

Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, de...

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Autores principales:	Matthew A Crawford, Marie D Burdick, Ian J Glomski, Anne E Boyer, John R Barr, Borna Mehrad, Robert M Strieter, Molly A Hughes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/21227b36da004736b44cb86f75972053
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spelling	oai:doaj.org-article:21227b36da004736b44cb86f759720532021-11-18T06:05:17ZInterferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.1553-73661553-737410.1371/journal.ppat.1001199https://doaj.org/article/21227b36da004736b44cb86f759720532010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21124994/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms.Matthew A CrawfordMarie D BurdickIan J GlomskiAnne E BoyerJohn R BarrBorna MehradRobert M StrieterMolly A HughesPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 11, p e1001199 (2010)
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 Matthew A Crawford Marie D Burdick Ian J Glomski Anne E Boyer John R Barr Borna Mehrad Robert M Strieter Molly A Hughes Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.
description	Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms.
format	article
author	Matthew A Crawford Marie D Burdick Ian J Glomski Anne E Boyer John R Barr Borna Mehrad Robert M Strieter Molly A Hughes
author_facet	Matthew A Crawford Marie D Burdick Ian J Glomski Anne E Boyer John R Barr Borna Mehrad Robert M Strieter Molly A Hughes
author_sort	Matthew A Crawford
title	Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.
title_short	Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.
title_full	Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.
title_fullStr	Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.
title_full_unstemmed	Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.
title_sort	interferon-inducible cxc chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/21227b36da004736b44cb86f75972053
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Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection.

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