Lack of group X secreted phospholipase A 2 increases survival following pandemic H1N1 influenza infection

The role of Group X secreted phospholipase A 2 (GX-sPLA 2 ) during influenza infection has not been previously investigated. We examined the role of GX-sPLA 2 during H1N1 pandemic influenza infection in a GX-sPLA 2 gene targeted mouse (GX −/− ) model and found that survival after infection was significantly greater in GX −/− mice than in GX +/+ mice. Downstream products of GX-sPLA 2 activity, PGD 2 , PGE 2 , LTB 4 , cysteinyl leukotrienes and Lipoxin A 4 were significantly lower in GX −/− mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX −/− mice. Based on the central role of sPLA 2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA 2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA 2 may be a potential therapeutic target during influenza. Highlights • We investigated GX-sPLA 2 −/− mice infected with pandemic H1N1. • GX −/− mice had increased survival and significantly lower eicosanoids in BAL fluid. • Lung RNA analysis identified earlier and increased induction of T and B cell responses in GX −/− mice. • GX may initiate influenza inflammation; inhibition promotes adaptive immunity and survival. • Our findings suggest that GX-sPLA 2 may be a potential therapeutic target during influenza.