Induction of iNOS expression and antimicrobial activity by interferon (IFN)-beta is distinct from IFN-gamma in Burkholderia pseudomallei-infected mouse macrophages.
Burkholderia pseudomallei is a causative agent of melioidosis. This Gram-negative bacterium is able to survive and multiple inside both phagocytic and nonphagocytic cells. We previously reported that exogenous interferons (both type I and type II) enhanced antimicrobial activity of the macrophages infected with B. pseudomallei by up-regulating inducible nitric oxide synthase (iNOS). This enzyme thus plays an essential role in controlling intracellular growth of bacteria. In the present study we extended our investigation, analysing the mechanism(s) by which the two types of interferons (IFNs) regulate antimicrobial activity in the B. pseudomallei-infected macrophages. Mouse macrophage cell line (RAW 264.7) that was exposed simultaneously to B. pseudomallei and type I IFN (IFN-beta) expressed high levels of iNOS, leading to enhanced intracellular killing of the bacteria. However, neither enhanced iNOS expression nor intracellular bacterial killing was observed when the macrophages were preactivated with IFN-beta prior to being infected with B. pseudomallei. On the contrary, the timing of exposure was not critical for the type II IFN (IFN-gamma) because when the cells were either prestimulated or co-stimulated with IFN-gamma, both iNOS expression and intracellular killing capacity were enhanced. The differences by which these two IFNs regulate antimicrobial activity may be related to the fact that IFN-gamma was able to induce more sustained interferon regulatory factor-1 (IRF-1) expression compared with the cells activated with IFN-beta.
Utaisincharoen
P
P
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand. scput@mahidol.ac.th
Anuntagool
N
N
Arjcharoen
S
S
Limposuwan
K
K
Chaisuriya
P
P
Sirisinha
S
S
D000818:Animals; D016957:Burkholderia pseudomallei; D002452:Cell Count; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D015151:Immunoblotting; D050856:Interferon Regulatory Factor-1; D016899:Interferon-beta / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008554:Melioidosis / Q000276:immunology*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D016899:Interferon-beta; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse