5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.
5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.
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DOI：
10.1371/journal.pone.0031701
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Medeiros AI
中科院分区：
文献类型：
--
作者：
Secatto A;Rodrigues LC;Serezani CH;Ramos SG;Dias-Baruffi M;Faccioli LH;Medeiros AI
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.
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