LSC Abstract – The expression and function of BPIFA1 in the pulmonary innate immune response to influenza A virus infection

BPIFA1 is a member the bactericidal/permeability-increasing (BPI) protein family and is structurally similar to other BPIF family members with demonstrated innate immune roles. It is produced mainly in the mammalian respiratory tract and has been implicated in airway host defense against respiratory pathogens. However, the function of this protein is yet unresolved in many species and by elucidating this will aid to clarify its physiological role within the lungs. The objective of this study was to assess BPIFA1 expression and function in the respiratory tract in response to Influenza A virus. Using BPIFA1 knockout mice, we have shown increased virus load and inflammation in the lungs of these mice infected with the X31 strain (H3N2) as compared with wild-type controls. Interestingly, there were large peri-vascular aggregations of B cells in the lungs of BPIFA1 -/- mice suggesting a role of BPIFA1 in modulating antibody responses. Lung tissues from mice infected with different strains of varying pathogenicities of Influenza A virus were analysed by immunohistochemical methods at specific time points during the infection period. Imaging software was then used to quantify the level of protein expression within the respiratory epithelium. It was found that the level of BPIFA1 decreased in response to highly pathogenic H5N1 and H7N9 infections but not to low pathogenicity H5N1 or H1N1 viruses. This alteration in expression was associated with an inflammatory response within the respiratory tissue surrounding the epithelium. Our data indicate that BPIFA1 influences inflammation and possibly signals to immune cells during Influenza A virus infection.