Abstract
It is possible that the difference in virulence and prevalence of different strains of Mycobacterium tuberculosis is related to the diverse immune response they evoke in the host. Outbreak strains have been shown to subvert the innate immune response as a potential host evasion mechanism. However, the immunological outcome of the interactions of different clinical strains with different host cells is still not understood. Extremely Drug Resistant (XDR) Beijing, a modern lineage clinical strain and a comparator ancient lineage strain, EAI-5, were selected for the present study. The early induction of proinflammatory cytokines in human peripheral blood monocyte derived macrophages (MDM), monocyte derived dendritic cells (MDDC) and whole blood (WB) infected by selected clinical isolates and laboratory strains H37Rv and BCG were assessed. The two clinical strains exhibited distinct patterns of cytokine induction. The ancient lineage strain induced substantially higher expression of all proinflammatory cytokines like TNF-α, IL-1β, IL-12 and chemokines like MCP-1, IL-8. However, the modern lineage strain exhibited suppressed response for the same. Further, the immune responses to two strains were conserved in infected MDM, MDDC and WB i.e. showing similar patterns of response across multiple human hosts. However, the differential response pattern was not observed when bacterial sonicates were used instead of live mycobacteria. The lineage specific patterns in induction of proinflammatory cytokines and chemokines by different M. tuberculosis strains remain similar in macrophage and dendritic cells isolated from different individuals. The present study also confirms that whole cell sonicates of different lineages of M. tuberculosis fail to induce such lineage specific response.
Highlights
It is possible that the difference in virulence and prevalence of different strains of Mycobacterium tuberculosis is related to the diverse immune response they evoke in the host
The percentages of infected cells were measured 4 hours after infection in monocyte derived macrophages (MDM) and monocyte derived dendritic cells (MDDC) isolated from Peripheral blood mononuclear cells (PBMC) of a particular individual by examination under acid-fast staining
It was observed that mRNA for proinflammatory cytokines, TNF-α, IL1β and IL-12, were expressed at high levels preferentially by Mycobacterium tuberculosis (MTB)-infected MDM, whereas MDDC produced comparatively lower levels of these cytokines except for IL-12
Summary
It is possible that the difference in virulence and prevalence of different strains of Mycobacterium tuberculosis is related to the diverse immune response they evoke in the host. The early induction of proinflammatory cytokines in human peripheral blood monocyte derived macrophages (MDM), monocyte derived dendritic cells (MDDC) and whole blood (WB) infected by selected clinical isolates and laboratory strains H37Rv and BCG were assessed. Conclusions: The lineage specific patterns in induction of proinflammatory cytokines and chemokines by different M. tuberculosis strains remain similar in macrophage and dendritic cells isolated from different individuals. Several different innate immune parameters were monitored for infection of THP-1 cells (monocytic leukemia cell line) with three drug resistance clinical isolates from different lineages of MTB and the infected cells showed lineage specific innate immune responses [8].
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