5-Lipoxygenase Deficiency Impairs Innate and Adaptive Immune Responses during Fungal Infection


Autoria(s): Secatto, Adriana; Rodrigues, Lilian Cataldi; Serezani, Carlos Henrique; Ramos, Simone Gusmao; Dias-Baruffi, Marcelo; Faccioli, Lucia Helena; Medeiros, Alexandra Ivo de
Contribuinte(s)

Universidade Estadual Paulista (UNESP)

Data(s)

20/05/2014

20/05/2014

20/03/2012

Resumo

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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.

Formato

9

Identificador

http://dx.doi.org/10.1371/journal.pone.0031701

Plos One. San Francisco: Public Library Science, v. 7, n. 3, p. 9, 2012.

1932-6203

http://hdl.handle.net/11449/42431

10.1371/journal.pone.0031701

WOS:000303855700003

WOS000303855700003.pdf

Idioma(s)

eng

Publicador

Public Library Science

Relação

PLOS ONE

Direitos

openAccess

Tipo

info:eu-repo/semantics/article