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Burkholderia pseudomallei Interferes with Inducible Nitric Oxide Synthase (iNOS) Production: A Possible Mechanism of Evading Macrophage Killing
Author(s) -
Utaisincharoen Pongsak,
Tangthawornchaikul Nattaya,
Kespichayawattana Wanapa,
Chaisuriya Predawan,
Sirisinha Stitaya
Publication year - 2001
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2001.tb02623.x
Subject(s) - burkholderia pseudomallei , melioidosis , microbiology and biotechnology , biology , macrophage , nitric oxide synthase , tumor necrosis factor alpha , bacteria , nitric oxide , immunology , biochemistry , genetics , in vitro , endocrinology
Burkholderia pseudomallei is a causative agent of melioidosis, a life threatening disease which affects humans and animals in tropical and subtropical areas. This bacterium is known to survive and multiply inside cells such as macrophages. The mechanism of host defense against this bacterium is still unknown. In this study, we demonstrated that B. pseudomallei exhibited unique macrophage activation activity compared with Escherichia coli and Salmonella typhi . The mouse macrophage cell line (RAW 264.7) infected with B. pseudomallei at MOI of 0.1:1, 1:1 and 10:1 did not express a detectable level of inducible nitric oxide synthase (iNOS). Moreover, the B. pseudomallei infected cells released TNF‐α only when they were infected with high MOI (10:1). Unlike the cells infected with B. pseudomallei , the cells infected with E. coli , and S. typhi expressed iNOS even at MOI of 0.1:1. These infected cells also released a significantly higher level of TNF‐α at the low MOI ratio. The cells that were preactivated with IFN‐γ prior to being infected with B. pseudomallei exhibited an enhanced production of iNOS and TNF‐α release. The increased macrophage activation activity in the presence of IFN‐γ also correlated with the restriction of the intracellular bacteria survival. Moreover, IFN‐γ also prevented cell fusion and multinucleated cell formation induced by B. pseudomallei , a phenomenon recently described by our group. Altogether, these results indicate that internalization of B. pseudomallei failed to trigger substantial macrophage activation, a phenomenon which could prolong their survival inside the phagocytic cells and facilitate a direct cell to cell spreading of B. pseudomallei to neighboring cells.