Cytosolic phospholipase A2 contributes to innate immune defense against Candida albicans lung infection

BMC Immunology

Research Article

Moumita Ghosh¹  HeeJung Lee¹  Sabarirajan Jayaraja¹  Elizabeth F. Redente¹  Bogeon Yun¹  Azzeddine Dakhama¹  Christina C. Leslie²  Charis L. Uhlson³  Robert C. Murphy³ 

[1] Department of Pediatrics, National Jewish Health, 1400 Jackson St., 80206, Denver, Colorado, USA;Department of Pediatrics, National Jewish Health, 1400 Jackson St., 80206, Denver, Colorado, USA;Department of Pharmacology, University of Colorado Denver, Aurora, Colorado, USA;Department of Pathology, University of Colorado Denver, Aurora, Colorado, USA;Department of Pharmacology, University of Colorado Denver, Aurora, Colorado, USA;

关键词: Cytosolic phospholipase A;    Prostaglandins;    Leukotrienes;    Neutrophils;    Macrophages;    Inflammation;    Candida albicans;   

DOI  :  10.1186/s12865-016-0165-9

 received in 2016-05-02, accepted in 2016-07-25,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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 A2 (cPLA2α) 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 cPLA2α and eicosanoids in regulating C. albicans lung infection is not understood.MethodsThe responses of cPLA2α+/+ and cPLA2α−/− 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 cPLA2α+/+ and cPLA2α−/− mice to recognize and kill C. albicans was also compared.ResultsAfter C. albicans instillation, cPLA2α+/+ 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 cPLA2α−/− mice, weight loss continued for 72 h, C. albicans was not completely cleared from the lung and disseminated to the kidneys. cPLA2α−/− 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 B2 and prostaglandin E2 were significantly lower in bronchoalveolar lavage fluid from C. albicans-infected cPLA2α−/− mice compared to cPLA2α+/+ mice. Alveolar macrophages and neutrophils from uninfected cPLA2α−/− mice exhibited less killing of C. albicans in vitro than cells from cPLA2α+/+ mice. In addition alveolar macrophages from cPLA2α−/− mice isolated 6 h after instillation of GFP-C. albicans contained fewer internalized fungi than cPLA2α+/+ macrophages.ConclusionsThe results demonstrate that cPLA2α contributes to immune surveillance and host defense in the lung to prevent infection by the commensal fungus C. albicans and to dampen inflammation.

【 授权许可】

CC BY   
© The Author(s). 2016