Host-Pathogen Interactions in a Failing Global lineage of MTBC:M.africanum

Tuberculosis (TB) remains a public health problem in resource limited settings such as Mali. Tuberculosis is caused by a slow-growing acid-fast bacillus; the initial acute infection being typically followed by a period of latency in about 95% of the cases and only a few will develop active disease. So far efforts to control TB are hampered by difficulties with prevention, diagnosis, and treatment. The immune response to TB is complex and not yet characterized completely which is making difficult the development of new vaccines and drugs. The innate immune system is a key factor in disease outcome. Although advantages of infection could be attributed to intrinsic characteristics of the pathogen, the host response needs to be defined to understand the outcome of the disease. Interferons (IFNs) are proteins made and released by host cells in response to the presence of pathogens such as bacteria, viruses, parasites or tumor cells. They activated immune cells such as natural killer cells and macrophages. Human monocytes derived from PBMCs are key cell components of the innate immune system that encounter the mycobacteria and are involved in the formation of Granuloma. To better understand responses due to host-pathogen interaction related to the outcome of TB disease, we will investigate the secretion of inflammatory cytokines. Recently, we identified by spoligotyping that Maf and Mtb are the most prevalent strains, respectively accounting for 27.8 and 71.4% of TB cases in Mali. Since its description by Castets et al. In 1968, Maf is an important cause of human tuberculosis (up to 40% of pulmonary tuberculosis) in West-Africa. M.africanum causes TB almost exclusively in countries between and including the Gambia and Cameroon. Although studies performed in and around West African countries about Maf have shown variable prevalence’s, all suggested that it is less common among drug resistant isolates and retreatment cases. Our preliminary report suggests that MAF is less likely to be resistant to TB first line drugs and less likely to be associated with treatment/retreatment failure than is MTB.