Host determinants of TB disease as targets for HDTs development: A study protocol

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health challenge. New diagnostic and therapeutic strategies are required to curb TB transmission. Here we outline a protocol to validate inflammatory proteins as potential biomarkers of TB disease and to evaluate the candidate genes as potential targets for host-directed therapy (HDT) development. Blood will be isolated from healthy, latent TB infected (LTBI) individuals and TB patients, and expression profiles of genes of interest will be determined using qPCR. A human monocytic cell line will be utilized to knock down genes of interest and to evaluate their contribution to Mtb infection. Pharmaceutical interception of target genes will be performed in peripheral blood mononuclear cells (PBMCs) infected with Mtb. This work will result in identification of TB associated inflammatory markers that can also be targeted for HDT development.