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Influenza A Virus Infection Predisposes Hosts to Secondary Infection with
Different Streptococcus pneumoniae Serotypes with Similar Outcome but
Serotype-Specific Manifestation
#MMPMID27647871
Sharma-Chawla N
; Sender V
; Kershaw O
; Gruber AD
; Volckmar J
; Henriques-Normark B
; Stegemann-Koniszewski S
; Bruder D
Infect Immun
2016[Dec]; 84
(12
): 3445-3457
PMID27647871
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Influenza A virus (IAV) and Streptococcus pneumoniae are major causes of
respiratory tract infections, particularly during coinfection. The synergism
between these two pathogens is characterized by a complex network of dysregulated
immune responses, some of which last until recovery following IAV infection.
Despite the high serotype diversity of S. pneumoniae and the serotype replacement
observed since the introduction of conjugate vaccines, little is known about
pneumococcal strain dependency in the enhanced susceptibility to severe secondary
S. pneumoniae infection following IAV infection. Thus, we studied how
preinfection with IAV alters host susceptibility to different S. pneumoniae
strains with various degrees of invasiveness using a highly invasive serotype 4
strain, an invasive serotype 7F strain, and a carrier serotype 19F strain. A
murine model of pneumococcal coinfection during the acute phase of IAV infection
showed a significantly increased degree of pneumonia and mortality for all tested
pneumococcal strains at otherwise sublethal doses. The incidence and kinetics of
systemic dissemination, however, remained bacterial strain dependent.
Furthermore, we observed strain-specific alterations in the pulmonary levels of
alveolar macrophages, neutrophils, and inflammatory mediators ultimately
affecting immunopathology. During the recovery phase following IAV infection,
bacterial growth in the lungs and systemic dissemination were enhanced in a
strain-dependent manner. Altogether, this study shows that acute IAV infection
predisposes the host to lethal S. pneumoniae infection irrespective of the
pneumococcal serotype, while the long-lasting synergism between IAV and S.
pneumoniae is bacterial strain dependent. These results hold implications for
developing tailored therapeutic treatment regimens for dual infections during
future IAV outbreaks.
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