The focus of my research is the study of the immune response during human tuberculosis (TB); particularly cytokine responses to M. tuberculosis (MTB) and its components and their role in depressed anti-MTB defense mechanisms in the peripheral blood and at the site most commonly affected by TB, the lung.
More recently these studies have focused on identifying the contribution of both T-cell and macrophage apoptosis on host immune reactivity in HIV-infected and -uninfected persons with MTB infection/disease, and on identifying the mediators and mechanisms involved.
MTB infection remains a major source of morbidity and mortality worldwide. Yet immune mechanisms involved in preventing initial MTB infection to activate TB are only incompletly understood. Our previous experience using peripheral blood and lung mononuclear cells from TB patients and healty control subjects indicate that immune mechanisms involved in a lack of control of MTB infection likely are multiple, and involve diverse factors such as overproduction of cytokines associated with intense immune activation (TNF) suppressive cytokines (TGF, IL-10) and increased susceptibility of MTB-responsive T-cells newly recruited to the lung to apoptosis.
Studies currently ongoing in my lab are designed to establish the mechanisms involved in apoptosis of (MTB-responsive) T-cells and to identify whether and how cytokine-mediated pathways are involved in the process.