Mechanisms by which M. tuberculosis 13KDa lectin modulates human immune responses

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DESCRIPTION (provided by applicant): Mechanisms by which M. tuberculosis 13 kDa lectin modulates human immune responses Project Summary Study of novel proteins from Mycobacterium tuberculosis may be a critical step for improving diagnostic tools, therapies and immunoprophylaxis against tuberculosis (TB), one of the most prevalent infectious diseases wordwide. We have identified a 13 KDa ricin-like lectin from M. tuberculosis that was found to agglutinate red blood cells and induce cytokine expression by macrophages. Moreover, serum from active tuberculosis patients contained high levels of IgG against this lectin. In the present proposal, we aim to characterize the role of 13 KDa Mtb lectin on human immune responses. The specific aims of the study are to 1) characterize the innate immune response profile elicited by the 13 KDa Mtb lectin; 2) determine innate receptor(s) expressed on human APC involved in the recognition of 13 KDa Mtb lectin; 3) investigate the role of 13 KDa Mtb lectin in the infection/phagocytosis process of M. tuberculosis by human APC and 4) examine specific humoral and cellular immune responses against 13 KDa Mtb lectin in TB patients before and after antibiotic treatment. Our long-term goal is to determine whether 13 KDa Mtb ricin-like lectin plays a role in regulating human immune responses to TB focusing on it possible activity in controlling APC function. These studies could be important in revealing a new target for immunotherapy of tuberculosis. PUBLIC HEALTH RELEVANCE: Mechanisms by which M. tuberculosis 13 kDa lectin modulates human immune responses Project Narrative Development of this project may impact human health because understanding of interactions between Mycobacteria and human cells could be important in revealing novel targets for immunotherapy of tuberculosis as well as disease biomarkers.