Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.

Pertussis (whooping cough) is frequently complicated by concomitant infections with respiratory viruses. Here we report the effect of Bordetella pertussis infection on subsequent influenza virus (PR8) infection in mouse models and the role of pertussis toxin (PT) in this effect. BALB/c mice infected...

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Autores principales:	Victor I Ayala, John R Teijaro, Donna L Farber, Susan G Dorsey, Nicholas H Carbonetti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/972e2221e6ab4a44b601ae3deebeb894
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spelling	oai:doaj.org-article:972e2221e6ab4a44b601ae3deebeb8942021-11-18T06:55:27ZBordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.1932-620310.1371/journal.pone.0019016https://doaj.org/article/972e2221e6ab4a44b601ae3deebeb8942011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21533103/?tool=EBIhttps://doaj.org/toc/1932-6203Pertussis (whooping cough) is frequently complicated by concomitant infections with respiratory viruses. Here we report the effect of Bordetella pertussis infection on subsequent influenza virus (PR8) infection in mouse models and the role of pertussis toxin (PT) in this effect. BALB/c mice infected with a wild-type strain of B. pertussis (WT) and subsequently (up to 14 days later) infected with PR8 had significantly increased pulmonary viral titers, lung pathology and mortality compared to mice similarly infected with a PT-deficient mutant strain (ΔPT) and PR8. Substitution of WT infection by intranasal treatment with purified active PT was sufficient to replicate the exacerbating effects on PR8 infection in BALB/c and C57/BL6 mice, but the effects of PT were lost when toxin was administered 24 h after virus inoculation. PT had no effect on virus titers in primary cultures of murine tracheal epithelial cells (mTECs) in vitro, suggesting the toxin targets an early immune response to increase viral titers in the mouse model. However, type I interferon responses were not affected by PT. Whole genome microarray analysis of gene expression in lung tissue from PT-treated and control PR8-infected mice at 12 and 36 h post-virus inoculation revealed that PT treatment suppressed numerous genes associated with communication between innate and adaptive immune responses. In mice depleted of alveolar macrophages, increase of pulmonary viral titers by PT treatment was lost. PT also suppressed levels of IL-1β, IL-12, IFN-γ, IL-6, KC, MCP-1 and TNF-α in the airways after PR8 infection. Furthermore PT treatment inhibited early recruitment of neutrophils and NK cells to the airways. Together these findings demonstrate that infection with B. pertussis through PT activity predisposes the host to exacerbated influenza infection by countering protective innate immune responses that control virus titers.Victor I AyalaJohn R TeijaroDonna L FarberSusan G DorseyNicholas H CarbonettiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e19016 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Victor I Ayala John R Teijaro Donna L Farber Susan G Dorsey Nicholas H Carbonetti Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.
description	Pertussis (whooping cough) is frequently complicated by concomitant infections with respiratory viruses. Here we report the effect of Bordetella pertussis infection on subsequent influenza virus (PR8) infection in mouse models and the role of pertussis toxin (PT) in this effect. BALB/c mice infected with a wild-type strain of B. pertussis (WT) and subsequently (up to 14 days later) infected with PR8 had significantly increased pulmonary viral titers, lung pathology and mortality compared to mice similarly infected with a PT-deficient mutant strain (ΔPT) and PR8. Substitution of WT infection by intranasal treatment with purified active PT was sufficient to replicate the exacerbating effects on PR8 infection in BALB/c and C57/BL6 mice, but the effects of PT were lost when toxin was administered 24 h after virus inoculation. PT had no effect on virus titers in primary cultures of murine tracheal epithelial cells (mTECs) in vitro, suggesting the toxin targets an early immune response to increase viral titers in the mouse model. However, type I interferon responses were not affected by PT. Whole genome microarray analysis of gene expression in lung tissue from PT-treated and control PR8-infected mice at 12 and 36 h post-virus inoculation revealed that PT treatment suppressed numerous genes associated with communication between innate and adaptive immune responses. In mice depleted of alveolar macrophages, increase of pulmonary viral titers by PT treatment was lost. PT also suppressed levels of IL-1β, IL-12, IFN-γ, IL-6, KC, MCP-1 and TNF-α in the airways after PR8 infection. Furthermore PT treatment inhibited early recruitment of neutrophils and NK cells to the airways. Together these findings demonstrate that infection with B. pertussis through PT activity predisposes the host to exacerbated influenza infection by countering protective innate immune responses that control virus titers.
format	article
author	Victor I Ayala John R Teijaro Donna L Farber Susan G Dorsey Nicholas H Carbonetti
author_facet	Victor I Ayala John R Teijaro Donna L Farber Susan G Dorsey Nicholas H Carbonetti
author_sort	Victor I Ayala
title	Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.
title_short	Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.
title_full	Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.
title_fullStr	Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.
title_full_unstemmed	Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.
title_sort	bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/972e2221e6ab4a44b601ae3deebeb894
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Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.

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