Influenza A virus exacerbates Staphylococcus aureus pneumonia in mice by attenuating antimicrobial peptide production.
Influenza A represents a significant cause of morbidity and mortality worldwide. Bacterial complications of influenza A confer the greatest risk to patients. TH17 pathway inhibition has been implicated as a mechanism by which influenza A alters bacterial host defense. Here we show that preceding influenza causes persistent Staphylococcus aureus infection and suppression of TH17 pathway activation in mice. Influenza does not inhibit S. aureus binding and uptake by phagocytic cells but instead attenuates S. aureus induced TH17 related antimicrobial peptides necessary for bacterial clearance in the lung. Importantly, exogenous lipocalin 2 rescued viral exacerbation of S. aureus infection and decreased free iron levels in the bronchoalveolar lavage from mice coinfected with S. aureus and influenza. These findings indicate a novel mechanism by which influenza A inhibits TH17 immunity and increases susceptibility to secondary bacterial pneumonia. Identification of new mechanisms in the pathogenesis of bacterial pneumonia could lead to future therapeutic targets.
Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
Keven M
KM
Robinson
Kevin J
KJ
McHugh
Sivanarayana
S
Mandalapu
Michelle E
ME
Clay
Benjamin
B
Lee
Erich V
EV
Scheller
Richard I
RI
Enelow
Yvonne R
YR
Chan
Jay K
JK
Kolls
John F
JF
Alcorn
D000704:Analysis of Variance; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000382:microbiology / Q000821:virology; D060085:Coinfection / Q000382:microbiology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000382:microbiology* / Q000821:virology; D011023:Pneumonia, Staphylococcal / Q000276:immunology / Q000382:microbiology* / Q000821:virology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity; D058504:Th17 Cells
D023181:Antimicrobial Cationic Peptides
Staphylococcal aureus; TH17; coinfection; host defense; influenza A; pneumonia