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2011 ; 6
(4
): e19016
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Bordetella pertussis infection exacerbates influenza virus infection through
pertussis toxin-mediated suppression of innate immunity
#MMPMID21533103
Ayala VI
; Teijaro JR
; Farber DL
; Dorsey SG
; Carbonetti NH
PLoS One
2011[Apr]; 6
(4
): e19016
PMID21533103
show ga
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 (?PT) 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-1?, IL-12, IFN-?, IL-6, KC, MCP-1 and TNF-?
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.