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Influenza infection suppresses NADPH oxidase-dependent phagocytic bacterial
clearance and enhances susceptibility to secondary methicillin-resistant
Staphylococcus aureus infection
#MMPMID24563256
Sun K
; Metzger DW
J Immunol
2014[Apr]; 192
(7
): 3301-7
PMID24563256
show ga
Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a leading
contributor to mortality during recent influenza pandemics. The mechanism for
this influenza-induced susceptibility to secondary S. aureus infection is poorly
understood. In this study, we show that innate antibacterial immunity was
significantly suppressed during the recovery stage of influenza infection, even
though MRSA superinfection had no significant effect on viral burdens. Compared
with mice infected with bacteria alone, postinfluenza MRSA-infected mice
exhibited impaired bacterial clearance, which was not due to defective phagocyte
recruitment, but rather coincided with reduced intracellular reactive oxygen
species levels in alveolar macrophages and neutrophils. NADPH oxidase is
responsible for reactive oxygen species production during phagocytic bacterial
killing, a process also known as oxidative burst. We found that
gp91(phox)-containing NADPH oxidase activity in macrophages and neutrophils was
essential for optimal bacterial clearance during respiratory MRSA infections. In
contrast to wild-type animals, gp91(phox-/-) mice exhibited similar defects in
MRSA clearance before and after influenza infection. Using gp91(phox+/-) mosaic
mice, we further demonstrate that influenza infection inhibits a cell-intrinsic
contribution of NADPH oxidase to phagocyte bactericidal activity. Taken together,
our results establish that influenza infection suppresses NADPH oxidase-dependent
bacterial clearance and leads to susceptibility to secondary MRSA infection.
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