Abstract
Bacterial lung infections are normally self-resolving in immunocompetent individuals, but can become severe in the co-infection setting, where respiratory viruses such as influenza can cause bacterial super-infections. Previous research in cancer has characterised an immune-suppressive phenotype of neutrophils; however, this cell population is poorly defined in the lung in co-infection setting. In our current study, we found that co-infection with Streptococcus pneumoniae and influenza A virus (IAV) caused persistent pneumococcal lung infection and excessive neutrophilic inflammation in mice that failed to resolve over 11 days post infection. Neutrophils isolated from the BALF of IAV-infected and co-infected mice demonstrated an immunosuppressive phenotype at day 7, with significantly higher expression of IL-10, Arg1 and iNOS. The phenotypic change towards immunosuppression was associated with a sustained increase in circulating Serum Amyloid A (SAA) in vivo, which has been reported to govern the emergence of immunosuppressive neutrophils in melanoma. At a molecular level, elevated SAA in circulation and the liver as a primary site of secretion was associated with increased IL-22 production in the lungs and increased STAT3 activation in the liver of co-infected mice. In summary, we have identified a novel mechanism by which the persistence of immunosuppressive neutrophils during co-infection results in the loss of bacterial clearance and more severe pneumococcal disease.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA2377.
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- Copyright ©the authors 2019