Article ; Online: Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxin-mediated suppression of innate immunity.
PloS one
2011 Volume 6, Issue 4, Page(s) e19016
Abstract: ... viruses. Here we report the effect of Bordetella pertussis infection on subsequent influenza virus (PR8 ... predisposes the host to exacerbated influenza infection by countering protective innate immune ... BL6 mice, but the effects of PT were lost when toxin was administered 24 h after virus inoculation. PT ...
| Abstract | 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. |
|---|---|
| MeSH term(s) | Animals ; Cytokines/metabolism ; Gene Expression ; Immunity, Innate/drug effects ; Lung/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Oligonucleotide Array Sequence Analysis ; Orthomyxoviridae Infections/complications ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/physiopathology ; Pertussis Toxin/immunology ; Pertussis Toxin/pharmacology ; Virus Replication ; Whooping Cough/complications |
| Chemical Substances | Cytokines ; Pertussis Toxin (EC 2.4.2.31) |
| Language | English |
| Publishing date | 2011-04-20 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ISSN | 1932-6203 |
| ISSN (online) | 1932-6203 |
| DOI | 10.1371/journal.pone.0019016 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.
Inter-library loan at ZB MED
Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.