Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates.

Abstract:

:Phagocytosis and mechanisms of killing of Aspergillus fumigatus conidia by murine alveolar macrophages (AM), which are the main phagocytic cells of the innate immunity of the lung, were investigated. Engulfment of conidia by murine AM lasts 2 h. Killing of A. fumigatus conidia by AM begins after 6 h of phagocytosis. Swelling of the conidia inside the AM is a prerequisite for killing of conidia. The contributions of NADPH oxidase and inducible nitric oxide synthase to the conidicidal activity of AM were studied using AM from OF1, wild-type and congenic p47phox(-/-) 129Sv, and wild-type and congenic iNOS(-/-) C57BL/6 mice. AM from p47phox(-/-) mice were unable to kill A. fumigatus conidia. Inhibitors of NADPH oxidase that decreased the production of reactive oxidant intermediates inhibited the killing of A. fumigatus without altering the phagocytosis rate. In contrast to NADPH oxidase, nitric oxide synthase does not play a role in killing of conidia. Corticosteroids did not alter the internalization of conidia by AM but did inhibit the production of reactive oxidant intermediates and the killing of A. fumigatus conidia by AM. Impairment of production of reactive oxidant intermediates by corticosteroids is responsible for the development of invasive aspergillosis in immunosuppressed mice.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Philippe B,Ibrahim-Granet O,Prévost MC,Gougerot-Pocidalo MA,Sanchez Perez M,Van der Meeren A,Latgé JP

doi

10.1128/iai.71.6.3034-3042.2003

keywords:

subject

Has Abstract

pub_date

2003-06-01 00:00:00

pages

3034-42

issue

6

eissn

0019-9567

issn

1098-5522

journal_volume

71

pub_type

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