Cytosolic phospholipase A(2) contributes to innate immune defense against Candida albicans lung infection

BACKGROUND: The lung is exposed to airborne fungal spores, and fungi that colonize the oral cavity such as Candida albicans, but does not develop disease to opportunistic fungal pathogens unless the immune system is compromised. The Group IVA cytosolic phospholipase A(2) (cPLA(2)α) is activated in response to Candida albicans infection resulting in the release of arachidonic acid for eicosanoid production. Although eicosanoids such as prostaglandins and leukotrienes modulate inflammation and immune responses, the role of cPLA(2)α and eicosanoids in regulating C. albicans lung infection is not understood. METHODS: The responses of cPLA(2)α(+/+) and cPLA(2)α(−/−) Balb/c mice to intratracheal instillation of C. albicans were compared. After challenge, we evaluated weight loss, organ fungal burden, and the recruitment of cells and the levels of cytokines and eicosanoids in bronchoalveolar lavage fluid. The ability of macrophages and neutrophils from cPLA(2)α(+/+) and cPLA(2)α(−/−) mice to recognize and kill C. albicans was also compared. RESULTS: After C. albicans instillation, cPLA(2)α(+/+) mice recovered a modest weight loss by 48 h and completely cleared fungi from the lung by 12 h with no dissemination to the kidneys. In cPLA(2)α(−/−) mice, weight loss continued for 72 h, C. albicans was not completely cleared from the lung and disseminated to the kidneys. cPLA(2)α(−/−) mice exhibited greater signs of inflammation including higher neutrophil influx, and elevated levels of albumin and pro-inflammatory cytokines/chemokines (IL1α, IL1β, TNFα, IL6, CSF2, CXCL1, CCL20) in bronchoalveolar lavage fluid. The amounts of cysteinyl leukotrienes, thromboxane B(2) and prostaglandin E(2) were significantly lower in bronchoalveolar lavage fluid from C. albicans-infected cPLA(2)α(−/−) mice compared to cPLA(2)α(+/+) mice. Alveolar macrophages and neutrophils from uninfected cPLA(2)α(−/−) mice exhibited less killing of C. albicans in vitro than cells from cPLA(2)α(+/+) mice. In addition alveolar macrophages from cPLA(2)α(−/−) mice isolated 6 h after instillation of GFP-C. albicans contained fewer internalized fungi than cPLA(2)α(+/+) macrophages. CONCLUSIONS: The results demonstrate that cPLA(2)α contributes to immune surveillance and host defense in the lung to prevent infection by the commensal fungus C. albicans and to dampen inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-016-0165-9) contains supplementary material, which is available to authorized users.