title: Group V secretory phospholipase A2 modulates phagosome maturation and regulates the innate immune response against Candida albicans.
abstract: Phospholipase A(2) (PLA(2)) hydrolyzes the sn-2 position of cell membrane phospholipids to release fatty acids and lysophospholipids. We have previously reported that group V secretory PLA(2) (sPLA(2)) 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 sPLA(2), phagosome maturation was reduced 50-60% at early time points while the binding of zymosan was unimpaired. The ability of group V sPLA(2) to regulate phagocytosis extended to phagocytosis of IgG- and complement-opsonized sheep RBC. Moreover, macrophages lacking group V sPLA(2) 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 sPLA(2). Furthermore, in a model of systemic candidiasis, mice lacking group V sPLA(2) had an increased fungal burden in the kidney, liver, and spleen at day 7 postinfection and increased mortality. Thus, group V sPLA(2) regulates phagocytosis through major phagocytic receptors and contributes to the innate immune response against C. albicans by regulating phagocytosis and killing through a mechanism that is likely dependent on phagolysosome fusion.
authors.affiliation: Department of Medicine, Harvard Medical School, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA. bbalestrieri@rics.bwh.harvard.edu
authors.forename: Barbara
authors.initials: B
authors.lastname: Balestrieri
authors.forename: Akiko
authors.initials: A
authors.lastname: Maekawa
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.forename: Howard R
authors.initials: HR
authors.lastname: Katz
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Arm