Immunomodulation and tolerance as a consequence of repeated or chronic infection

Upon repeated or chronic infection, the immune system can be trained to decrease its inflammatory response.

These changes enable some pathogens, such as malaria and tuberculosis to co-exist with the host with minimal impact on the host’s health.

In this project, our overall aim is to study how the immune system adapts to and controls infection without leading to symptomatic disease.

We have established unique cohorts of individuals with either clinical or asymptomatic malaria and clinical or asymptomatic tuberculosis. We will investigate these cohorts at an integrated systems level, cellular level, and molecular level.

Our systems immunology approach includes integrating proteomic data from plasma with transcriptomic, phenotypic, and functional peripheral blood cell data and identifying differences associated with symptomatic or asymptomatic infection.

We will then assess the effect of the inflammatory response on the B cell compartment, including CD11c+ B cell differentiation and antibody production. Antibody-NK cell interplay will then be evaluated functionally at bulk and single-cell resolution.

Finally, we will investigate the role of individual transcription factors and cellular proteins in B cells and monocytes responding to infection or in vitro stimulation.

Collectively, these experiments will improve our understanding of tolerance at the whole immune system level, the cellular level, and the molecular level.