Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection

The role of Group X secreted phospholipase A2(GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2during H1N1 pandemic influenza infection in a GX-sPLA2gene targeted mouse (GX−/−) model and found that survival after infection was significantly greater in GX−/−mice than in GX+/+mice. Downstream products of GX-sPLA2activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4were 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 sPLA2enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2may be a potential therapeutic target during influenza.