Alexander Panda, MD, MPH

Postdoctoral Fellow, Internal Medicine (pulmonary)

Thesis Advisor

Richard Bucala

Thesis Committee

Heather Allore
Alfred Bothwell
Margaret Pisani
Albert Shaw

Thesis Project

Age-Associated Alterations in Toll-Like Receptor Function in Human Dendritic Cells

Influenza remains an important cause of morbidity and mortality in older adults, who are more susceptible to severe infections and frequently respond poorly to vaccination. This is in part a consequence of the functional deterioration of the immune system with age. While age-associated alterations in the adaptive immune system have been identified, innate immunity remains incompletely understood in the setting of human aging. An important component of the innate immune system is a family of receptors known as Toll-like receptors (TLR). TLRs are able to bind to a wide variety of pathogens by recognition of phylogenetically well preserved pathogen-associated molecular patterns (PAMPs). Subsequent signaling through TLRs on antigen presenting cells is a crucial step in the activation of innate immunity as well as the ensuing mobilization of the adaptive immune system. Lab results demonstrate that TLR1 function in monocytes specifically deteriorates with aging and that the expression of co-stimulatory proteins such as CD80 and CD86 is defective in response to TLR activation in older individuals. Dr. Panda’s project intends to extend these findings by evaluating TLR function in peripheral blood dendritic cells (DC) and establish whether TLR function in vitro has clinical correlates, by evaluating if TLR function predicts influenza vaccine responses in older adults. Dr. Panda hypothesizes that TLR function of DCs declines with human aging, and that the decrease in immune responsiveness associated with aging is in part a consequence of a decline in function of one or more TLRs.