Differential activation of inflammasome contributes to
strain-specific pathogenesis of Mycobacterium tuberculosis in rabbits
Ranjeet Kumar*, Selvakumar Subbian*
*Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
Tuberculosis (TB) remains a global health concern due to high morbidity and mortality in patients worldwide. One of the critical aspects of efficient TB control is understanding genetic alterations and variability in pathogenicity of different clinical isolates of Mycobacterium tuberculosis (Mtb). Infection with CDC1551 induces early and strong pro-inflammatory cytokine response in human monocytes. Moreover, they generate more robust T cell activation in the lungs of infected mice. In contrast, infection with HN878 failed to stimulate CD4 T cell-mediated, Th-1 type immunity associated with induction of type -1 interferon signaling and poor host control of infection. In the present study, we explored the longitudinal genome-wide transcriptome analysis of rabbit lungs infected with clinical Mtb strains CDC1551 and HN878. Our findings suggest time-dependent variation in host gene expression profiles. Infection with HN878 regulated cellular framework reorganization that suppressed the host immune response. Compared to CDC1551, infection with HN878 upregulated the expression of genes involved in autophagy, host cell lipid, and small molecule metabolism. Based on the gene expression profiles from lung tissues, we tested the immune regulatory pathways in rabbit bone marrow-derived macrophages (BMM). We found activation of genes involved in inflammasome formation in HN878-infected BMM, compared to CDC1551-infected cells. Further analysis of inflammasome pathway regulation is warranted to determine its role in Mtb survival and disease progression.