Reduced TNF-α and IFN-γ responses to Central Asian strain 1 and Beijing isolates of Mycobacterium tuberculosis in comparison with H37Rv strain

Pakistan ranks eighth in terms of tuberculosis burden worldwide, with an incidence of 181/100 000. The predominant genotypes of Mycobacterium tuberculosis are reported to be the Central Asian strain 1 (CAS1) and Beijing families. Mycobacterium tuberculosis down-regulates host pro-inflammatory cytokines, which are essential for protection against infection. There is currently little information regarding the interaction of the CAS1 genotype with host cells. We studied the growth rates of CAS1 and Beijing clinical isolates, and their ability to induce cytokines compared with the laboratory reference strain H37Rv. Host responses were studied using a THP-1 monocytic cell line model and an ex vivo whole blood assay. Growth rates of CAS1 and Beijing isolates were significantly lower (P = 0.011) compared with H37Rv. All clinical isolates induced significantly lower levels of TNF-α secretion (P = 0.003) than H37Rv in THP-1 cells and in the whole blood assay of healthy donors (n = 8). They also induced lower IFN-γ secretion in the whole blood assay (P < 0.001). A positive correlation was observed between the growth indices (GI) of H37Rv, Beijing and CAS1 strains and the TNF-α responses they induced [Pearson's correlation coefficient (R2): 0.936, 0.775 and 0.55, respectively], and also between GI and IFN-γ production (R2: 0.422, 0.946, 0.674). These findings suggest that reduced growth rate, together with down-modulation of pro-inflammatory cytokines, is a contributory mechanism for the predominance of the CAS genotype.