Influenza A Virus Exacerbates Staphylococcus aureus Pneumonia in Mice by Attenuating Antimicrobial Peptide Production

Robinson, Keven M.; McHugh, Kevin J.; Mandalapu, Sivanarayana; Clay, Michelle E.; Lee, Benjamin; Scheller, Erich V.; Enelow, Richard I.; Chan, Yvonne R.; Kolls, Jay K.; Alcorn, John F.

doi:10.1093/infdis/jit527

Cited by 121 publications

(137 citation statements)

References 29 publications

(37 reference statements)

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“…4J), possibly due to the very high bacterial levels driving IL-6 production in the sfb-negative mice at this time point, while the sfb-positive mice were beginning to clear the infection. Th17 immunity leads to neutrophil attraction (25) and production of antimicrobial peptides (11). sfb-positive mice (both initially colonized mice and initially sfb-negative mice after cohousing with sfb-positive mice or after gavage with sfb) had larger numbers of Ly6G-positive cells (neutrophils) in BALF (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, mice with defects in Th17 signaling have impaired bacterial clearance from the lung after infection with Klebsiella pneumoniae (8). More recently, the Th17 pathway was implicated in the defense against S. aureus pneumonia as well (9)(10)(11). Mice lacking the interleukin-17 (IL-17) receptor or IL-22 or mice that were coinfected with influenza A virus and thereby deficient in type 17 immunity displayed impaired bacterial clearance of S. aureus compared to wild-type or influenza virus-free mice (10).…”

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confidence: 99%

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Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia

et al. 2015

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c Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22؉ TCR␤ ؉ cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection.

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Section: Resultsmentioning

confidence: 99%

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Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia

et al. 2015

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“…A number of reports have linked the development of increased inflammatory neutrophilia with an increased susceptibility of mice to superinfection at days 6 and 7 after influenza virus infection (15)(16)(17). Increased numbers of neutrophils in the lungs of superinfected animals compared to those in mice infected with either S. pneumoniae or S. aureus alone correlated with increased bacterial load and increased mortality; however, depletion of neutrophils did not improve or worsen the outcome of superinfection (15,18). Other work has demonstrated significant neutrophil accumulation in murine lungs in response to S. pneumoniae infection in mice infected with influenza virus for either 3 or 6 days as well as in mice not infected with influenza virus (19).…”

Section: Role Of Phagocytes In Host Susceptibility To Superinfectionmentioning

confidence: 99%

Influenza and Bacterial Superinfection: Illuminating the Immunologic Mechanisms of Disease

2015

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cSeasonal influenza virus infection presents a major strain on the health care system. Influenza virus infection has pandemic potential, which was repeatedly observed during the last century. Severe disease may occur in the young, in the elderly, in those with preexisting lung disease, and in previously healthy individuals. A common cause of severe influenza pathogenesis is superinfection with bacterial pathogens, namely, Staphylococcus aureus and Streptococcus pneumoniae. A great deal of recent research has focused on the immune pathways involved in influenza-induced susceptibility to secondary bacterial pneumonia. Both innate and adaptive antibacterial host defenses are impaired in the context of preceding influenza virus infection. The goal of this minireview is to highlight these findings and synthesize these data into a shared central theme of pathogenesis.

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“…We have previously shown that Lcn2 promotes clearance of S. aureus during influenza superinfection. 17 It is possible that the lung repairing after influenza is able to competently control S. aureus via antimicrobial peptide functions, despite decreased phagocyte recruitment.…”

Section: Recovery From Influenza Infectionmentioning

confidence: 99%

Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection

Pociask

Robinson

Chen

et al. 2017

The American Journal of Pathology

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Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild-to-moderate disease phenotypes and recover within a few weeks. Influenza is known to cause persistent alveolitis in animal models; however, little is known about the molecular pathways involved in this phenotype. We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathologic processes and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days after infection. Influenza induced persistent parenchymal lung inflammation, alveolar epithelial metaplasia, and epithelial endoplasmic reticulum stress that were evident after the clearance of virus and resolution of morbidity. Influenza infection induced robust changes in the lung transcriptome, including a significant impact on inflammatory and extracellular matrix protein expression. Despite the robust changes in lung gene expression, preceding influenza (21 days) did not exacerbate secondary Staphylococcus aureus infection. Finally, we examined the impact of influenza on miRNA expression in the lung and found an increase in miR-155. miR-155 knockout mice recovered from influenza infection faster than controls and had decreased lung inflammation and endoplasmic reticulum stress. These data illuminate the dynamic molecular changes in the lung in the weeks after influenza infection and characterize the repair process, identifying a novel role for miR-155. (Am J Pathol 2017, 187: 851e863; http://dx

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Influenza A Virus Exacerbates Staphylococcus aureus Pneumonia in Mice by Attenuating Antimicrobial Peptide Production

Cited by 121 publications

References 29 publications

Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia

Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia

Influenza and Bacterial Superinfection: Illuminating the Immunologic Mechanisms of Disease

Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection

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