Dr Peter Crompton
Room: Cairns D3.003, Townsville 145.032
Antibody responses to Plasmodium falciparum infection and candidate malaria vaccines are generally short-lived in children, leaving them susceptible to repeated bouts of febrile malaria.Long-lived antibody responses depend on memory B cells (MBCs) and long-lived plasma cells that arise from germinal centers in secondary lymphoid organs in a process that requires T follicular helper (Tfh) cells. In longitudinal studies in Mali, where malaria transmission is intense and seasonal, we are investigating the B cell and Tfh cell biology underlying the inefficient acquisition of humoral immunity to malaria. We find that chronic malaria exposure is associated with an increase in atypical MBCs that resemble B cells expanded in persistent viral infections. Atypical MBCs express an array of inhibitory receptors and their B cell receptor signaling is stunted resulting in impaired B cell responses including proliferation, cytokine production and antibody secretion. In separate but related studies, we find that Malian children at baseline have circulating PD-1+CXCR5+CD4+ T cells that resemble germinal center Tfh cells phenotypically and functionally, and that within this population the CXCR3- subset is superior to the Th1-polarized CXCR3+ subset in helping B cells. Longitudinally, acute malaria in the same children drives a Th1 cytokine response, and accordingly, the less-functional Th1-polarized CXCR3+ subset is preferentially activated and its activation does not correlate with B cell and antibody responses. These data provide insights into the B cell and Tfh cell biology underlying the inefficient acquisition of humoral immunity to malaria and point toward the possibility of modulating B cell and Tfh cell responses to enhance malaria vaccine efficacy in endemic areas.
Dr Peter Crompton Bio
Dr. Crompton received his M.D. and M.P.H. from The Johns Hopkins Schools of Medicine and Public Health in 2000. He then completed a residency in internal medicine at Massachusetts General Hospital/Harvard University in Boston before going on to a fellowship in infectious diseases at NIAID in 2004. After a year of clinical training at NIAID, he earned a diploma in tropical medicine and hygiene at the London School of Hygiene & Tropical Medicine before joining the Laboratory of Immunogenetics in 2005 to pursue his research interest in the human immune response to malaria. In 2010, he became a tenure-track investigator and chief of the Malaria Infection Biology and Immunity Unit. Dr. Crompton is certified in internal medicine and infectious disease by the American Board of Internal Medicine.