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.
Highlights
Tuberculosis (TB) continues to be a major infectious and deadly disease throughout the developing world
After washing with PBS, monocytes were cultured in RPMI-1640 medium supplemented with 10% heatinactivated human serum (Hyclone), 50 mg/ml penicillin-streptomycin (Invitrogen), and 40 ng/ml granulocyte-monocyte colonystimulating factor (GM-CSF; ProSpec-Tany TechnoGene, Ltd, East Brunswick, NJ, USA) at 37uC under a 5% CO2, humidified atmosphere
Comparing the levels of cytokine expression between ancient and modern Beijing lineages revealed that the ancient Beijing strains elicited significantly higher levels of IL-1b, IL-6, and IFN-c (Fig. 1)
Summary
Tuberculosis (TB) continues to be a major infectious and deadly disease throughout the developing world. It has been estimated that 13,000 new TB cases occur each year in Taiwan, based on statistics of the Center for Disease Control, Department of Health [1]. Both the incidence and mortality rates of TB have decreased steadily since 1950; it is still an immense public health problem and remains a serious infectious disease in Taiwan. Previous studies using human monocyte-derived macrophages (MDM) proved that modern lineages of MTB induce mild inflammatory responses whereas ancient lineages induce more robust responses [11,12] These results suggest that a reduced immune response to modern MTB lineages contributes to the more rapid disease progression they cause as well as their higher rates of transmission [11,12]
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