Influence of SP110 polymorphisms in human macrophages of pulmonary tuberculosis disease among Ugandans

Human macrophages are a cell type preferentially infected by Mycobacterium tuberculosis (Mtb), the biological agent which causes tuberculosis disease (TB), but can also be infected by HIV. Both Mtb and HIV induce host-immune responses to infection whose effectors are genes activated by other secreted proteins called interferons. One of these effector genes, the Speckled 110 kD (SP110), is highly expressed in human cells called macrophages, acting as a co-activator for the production of other cellular protective proteins and regulating cell differentiation. Studies suggest SP110 expression limits Mtb proliferation in macrophages but promotes HIV replication. Kyabaggu’s question is, do SP110 gene single nitrogenous base changes (single nuclear polymorphisms (SNPs)) influence susceptibility to Pulmonary TB (Ptb) infection and disease in Ugandans? He and his team aim to identify SP110 SNPs among Ugandan Ptb patients using next-generation DNA sequencing technology and determine the influence on susceptibility to disease. They will also investigate, by in vitro tissue culture and confocal microscopy or ELISA techniques, the relationship between SP110 SNPs with common Mtb lineages in Uganda; as well as with HIV. Results from the study may provide further insights into mechanisms of establishment and persistence of Mtb, and HIV, infection in human macrophages. Study results may also provide evidence of a link between SP110 SNPs and the high prevalence of TB-HIV co-infection among Ugandans. This knowledge would be relevant for design of improved preventive and therapeutic strategies capable of eliminating pathogen reservoirs in the host, a key element for the global campaigns to eliminate TB disease and effectively control HIV.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.