Influence of phenotypic and molecular characteristics on the growth of Mycobacterium tuberculosis and cytokine production in macrophage

Abstract

[한글]

[영문]A major research topic in the pathogenesis of tuberculosis is the characterization of the virulence determinants of Mycobacterium tuberculosis. The aim of this study was to determine whether previously-suggested virulent factors of M. tuberculosis strain genotype, drug-resistance and expression of the cell wall-derived virulent molecule phenolicglycolipid-tb (PGL-tb) affect the survival and immune response of clinical isolates.A total of 31 M. tuberculosis clinical isolates were characterized by spoligotyping, a drug susceptibility test (DST), and a dot-ELISA with an anti-PGL-tb specific monoclonal antibody. The mouse macrophage cell line J774A.1 was infected with a total of 12 M. tuberculosis strains selected based on genotypic and phenotypic results.Seven-day growth patterns with 1 multiplicity of infection (MOI), and cytokine levels were measured from macrophage cell supernatants and compared between non-Beijing vs. Beijing strains, drug-susceptible vs. drug-resistant strains, and non-PGL-tb vs. PGL-tb producers.We found that differences in strain genotype, drug-resistant, and PGL-tb did not contribute significantly to M. tuberculosis growth in macrophages, but these factors were significantly associated with release of TNF-α, IL-10, IL-12p70, and nitric oxide (NO) by macrophages in response to TB infection. Difference in these cytokine and NO production by macrophages between clinical isolates may influence on pathogenesis of M. tuberculosis infection in humans.