Open AccessBurkholderia pseudomallei-Induced Expression of a Negative Regulator, Sterile-α and Armadillo Motif-Containing Protein, in Mouse Macrophages: a Possible Mechanism for Suppression of the MyD88-Independent Pathway
Author(s) -
Matsayapan Pudla,
K. Limposuwan,
Pongsak Utaisincharoen
Publication year - 2011
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01254-10
Subject(s) - burkholderia pseudomallei , biology , armadillo , melioidosis , regulator , microbiology and biotechnology , burkholderia , genetics , bacteria , gene
Burkholderia pseudomallei , a causative agent of melioidosis, is a Gram-negative facultative intracellular bacterium that can survive and multiply in macrophages. Previously, we demonstrated thatB. pseudomallei failed to activate gene expression downstream of the MyD88-independent pathway, particularly the expression of beta interferon (IFN-β) and inducible nitric oxide synthase (iNOS), leading to the inability of macrophages to kill this bacterium. In the present report, we extended our study to show thatB. pseudomallei was able to activate sterile-α and Armadillo motif (SARM)-containing protein, a known negative regulator of the MyD88-independent pathway. Both liveB. pseudomallei and heat-killedB. pseudomallei were able to upregulate SARM expression in a time-dependent manner in mouse macrophage cell line RAW 264.7. The expression of SARM required bacterial internalization, as it could be inhibited by cytochalasin D. In addition, the intracellular survival ofB. pseudomallei was suppressed in SARM-deficient macrophages. Increased expression of IFN-β and iNOS and degradation of IκBα correlated with enhanced macrophage killing capability. These results demonstrated thatB. pseudomallei modulated macrophage defense mechanisms by upregulating SARM, thus leading to the suppression of IFN-β and iNOS needed for bacterial elimination.