5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.

Secatto A, Rodrigues LC, Serezani CH, Ramos SG, Dias-Baruffi M, Faccioli LH, Medeiros AI
PLoS One. 2012 7 (3): e31701

PMID: 22448213 · PMCID: PMC3308949 · DOI:10.1371/journal.pone.0031701

5-Lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO(-/-) mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO(-/-) mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.

MeSH Terms (21)

Animals Arachidonate 5-Lipoxygenase Cell Proliferation Cells, Cultured Cytotoxicity, Immunologic Flow Cytometry Histoplasma Histoplasmosis Immunity, Humoral Immunity, Innate Leukotriene B4 Leukotriene C4 Lung Lymphocyte Activation Macrophages, Peritoneal Mice Mice, Knockout Nitric Oxide Phagocytosis Survival Rate T-Lymphocytes

Connections (1)

This publication is referenced by other Labnodes entities: