Affiliation:
1. Department of Microbiology and Immunology, Weill Medical College of Cornell University, and Programs in Immunology and Microbial Pathogenesis and in Molecular Biology, Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10021
2. Departments of Chemistry and Biochemistry, University of Washington, Seattle, Washington 98195
Abstract
ABSTRACT
During the course of infection
Mycobacterium tuberculosis
predominantly resides within macrophages, where it encounters and is often able to resist the antibacterial mechanisms of the host. In this study, we assessed the role of macrophage phospholipases A
2
(PLA
2
s) in defense against
M. tuberculosis
. Mouse bone marrow-derived macrophages (BMDMs) expressed cPLA
2
-IVA, cPLA
2
-IVB, iPLA
2
-VI, sPLA
2
-IIE, and sPLA
2
-XIIA. The expression of cPLA
2
-IVA was increased in response to
M. tuberculosis
, gamma interferon, or their combination, and cPLA
2
-IVA mediated the release of arachidonic acid, which was stimulated by
M. tuberculosis
in activated, but not unactivated, macrophages. We confirmed that arachidonic acid is highly mycobactericidal in a concentration- and pH-dependent manner in vitro. However, when
M. tuberculosis
-infected macrophages were treated with PLA
2
inhibitors, intracellular survival of
M. tuberculosis
was not affected, even in inducible nitric oxide synthase-deficient macrophages, in which a major bactericidal mechanism is removed. Moreover, intracellular survival of
M. tuberculosis
was similar in cPLA
2
-IVA-deficient and wild-type macrophages. Our results demonstrate that the cytosolic PLA
2
s are not required by murine BMDMs to kill
M. tuberculosis
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
15 articles.
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