Voltage Gated Calcium Channels Negatively Regulate Protective Immunity to Mycobacterium tuberculosis

Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity

Contribution of Non-pharmacological Factors in Non-compliance of Dots Amongst Tuberculosis Patients

Background: One of the important factors in control of tuberculosis is non-compliance has role in multi-drug resistant tuberculosis, poor treatment outcome and cause increased morbidity and mortality of tuberculosis. Objective: This study explores the contribution of non-pharmacological factors in non-compliance of directly observed treatment short course among tuberculosis patients. Methodology: The Cross sectional prospective study was interviewed by using set of questionnaire with enrolled patients of TB at DOTS centre of LRS Institute of Tuberculosis and Respiratory disease New Delhi, India. The Patients who discontinue and interrupted treatment for more than 2 months were categorized as noncompliance cases. Results: Five hundred sixty six patients TB patients enrolled during the study out of which forty non-compliance cases we observed. various factors and their contribution in noncompliance, the nuclear family have contribution 40 %, living life style of three member family in one room set contribute 42.5% role in non-compliance and types of patients who was new found 35% contribution in non-compliance. Beside these 10% of non-compliance TB patient have positive influence to tuberculosis treatment, as family and social factors have 70 % negative influence in non-compliance as well as psychological and their positive influence to non-compliance in tuberculosis treatment were only 40%. Conclusion: Various factors contribute in non-compliance of tuberculosis treatment therefore more attention should be paid to psychological aspect in order to behavioral and life style modification during tuberculosis treatments