Immunogenomics

One of the most striking features of tuberculosis are its extremely widespread infection prevalence levels, with an estimation of ~30% of the world’s population being infected with its causative agent: the bacterium Mycobacterium tuberculosis (MTB). However, only ~10% of infected individuals will develop the disease during their lifetime, which points to the existence of major genetic factors contributing to inter-individual variation in TB susceptibility.

As a central part of my work in Dr. Barreiro’s lab in Montreal, I am interested in the identification of the genes and biological mechanisms that contribute to inter-individual variability in the response of human macrophages (Mfs) to MTB infection.

tb_immunogen_summary

Schematic illustration of the study design. The study subjects are grouped in two panels: subjects in panel S are TB susceptible, while a vast majority (~90%) of individuals in panel R can be considered TB-resistant. We extract blood samples from these 200 individuals, extract their genotypic profiles, and, in parallel, purify Macrophages and infect them with the same virulent strain of Mycobacterium tuberculosis. After infection, RNA-seq expression profiles, along with cytokine levels and bacterial clearance metrics are registered at different time-points after infection.

To do so, we purify human Mfs (the primary immune cells targeted by MTB in vivo) extracted from two panels of 100 healthy European-descent individuals that have, or have not, experienced TB in the past. Then, in collaboration with Dr. L. Tailleux, (Institute Pasteur, Paris), we infect these Mfs with a virulent strain of MTB, and measure a series of molecular phenotypes informing about the strengh of the Mfs in their response to MTB.

The main goals of the project span from the identification of genes whose response to infection depends on subjects’ susceptibility to TB to the identification of the underlying genotypic variants that represent risk factors to develop the disease.

 

 

 

 

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