The Pattern of Cytokine Production In Vitro Induced by Ancient and Modern Beijing Mycobacterium tuberculosis Strains

Abstract

It is unclear to what extent the host-responses elicited by Beijing versus non-Beijing strains of Mycobacterium tuberculosis (MTB) contribute to the predominance of modern Beijing strains in Taiwan and some other Asian countries. The purpose of this study was to compare the expression profiles of virulence-related genes in human monocyte-derived macrophages infected in vitro with Beijing (ancient and modern strains) and non-Beijing strains (EAI strains) of MTB that are epidemic in Taiwan. We found that modern Beijing strains induced lower levels of pro-inflammatory cytokines, whereas EAI strains induced higher levels. Notably, the most prevalent modern Beijing sub-lineage, possessing intact RD150 and RD142 chromosomal regions, induced very low levels of pro-inflammatory cytokines, especially interleukin-1β. Moreover, in an intracellular growth assay, the survival of the same modern Beijing strain in human monocyte-derived macrophages was significantly higher than that of an ancient Beijing strain and an EAI strain. Taken together, these results may explain why modern Beijing strains of MTB predominate in Taiwan.

Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese

“…For example, a recent study showed "modern" Beijing caused more histopathological changes and mortality in mice (56). Most of all, three more recent studies all found that "modern" Beijing strains induced lower and/or delayed proinflammatory that may enable the bacteria to escape from host immune response (57)(58)(59). Epidemiologically, numerous studies from various geographical settings have suggested a higher transmissibility of "modern" Beijing genotype, as indicated by increased prevalence in young people (i.e., a proxy for ongoing transmission) (12,23,51,60), or a higher genotypic clustering proportion than "ancient" genotype (26,52,55).…”

Mycobacterium tuberculosis: ecology and evolution of a human bacterium

“…In vivo experiments in animals, particularly in rabbits and mice, have shown that these strains are highly virulent, with increased dissemination and earlier death of the infected animals (Manca et al, 2001;Tsenova et al, 2005 that the host response against modern and ancestral MTB lineages is different (Chakraborty et al, 2013). Specifically, a more rapid disease progression and a more elevated transmission potential have been observed following infection by modern lineages (Portevin et al, 2011;Reiling et al, 2013;Chen et al, 2014). Based on these epidemiological and experimental data, it seems clear that MTB has evolved towards an increased transmission and virulence potential.…”

Sublineages of Mycobacterium tuberculosis Beijing genotype strains and unfavorable outcomes of anti-tuberculosis treatment

“…Disease caused by modern Beijing MTB strains conferred a risk of TB recurrence, despite having less frequent drug resistance than that caused by the ancient Beijing genotype. Previous reports indicate that modern Beijing strains produce lower levels of proinflammatory cytokines [37,38] and have a higher survival in macrophages [38] than ancient Beijing strains. These factors may facilitate persistent infection or reactivation from latent infection, although investigation of these properties at sublineage levels has only just begun.…”