Group V Secretory Phospholipase A2 Modulates Phagosome Maturation and Regulates the Innate Immune Response Against Candida albicans

摘要

Phospholipase A2 (PLA2) hydrolyzes the sn-2 position of cell membrane phospholipids to release fatty acids and lysophospholipids. We have previously reported that group V secretory PLA2 (sPLA2) translocates from the Golgi and recycling endosomes of mouse peritoneal macrophages to newly formed phagosomes and regulates the phagocytosis of zymosan, suggesting a role in innate immunity. Here we report that in macrophages lacking group V sPLA2 phagosome maturation was reduced 50–60% at early time points while the binding of zymosan was unimpaired. The ability of group V sPLA2 to regulate phagocytosis extended to phagocytosis of IgG- and complement-opsonized sheep red blood cells. Moreover, macrophages lacking group V sPLA2 had delays in phagocytosis, phagosome maturation and killing of Candida albicans. Cytokine production and eicosanoid generation were not impaired by the lack of group V sPLA2. Furthermore, in a model of systemic candidiasis, mice lacking group V sPLA2 had an increased fungal burden in the kidney, liver and spleen at day 7 post-infection and increased mortality. Thus, group V sPLA2 regulates phagocytosis through major phagocytic receptors and contributes to the innate immune response against Candida albicans by regulating phagocytosis and killing through a mechanism that is likely dependent on phagolysosome fusion.