Apoptotic microparticles and DC dysregulation in HIV

Dr Frleta works on the regulation of human dendritic cell (DC) function during inflammation resulting from cancer or infectious diseases such as HIV. DCs are critical sentinel cells of the immune system that bridge innate and adaptive immune responses. Specifically, DCs can present antigen to and activate downstream T cell immunity which is necessary for controlling disease. DCs have also been shown to activate B cells, NK cells, and other downstream mediators of protective immunity.
As well as inducing immunity, DCs also maintain tolerance to self antigen frequently by responding to signals from apoptotic cells which are generated during normal cell turnover. Such pathways are critical for preventing immune responses to self antigen and can be perturbed during autoimmunity or exploited during certain viral infections. Understanding how DCs are regulated by apoptotic cellular material, in the context of pathogen-derived stimuli, endogenous danger signals, or non-inflammatory environments is important for both elucidating DC function during disease as well as targeting DCs in therapuetic strategies. One such example is DC function during acute HIV-1 infection (AHI).

During AHI, DC function is dysregulated resulting in poor controlling immunity towards HIV-1. Dr Dr Frleta’s work focuses on mechanisms by which DCs are inhibited during AHI. He has found that during the early part of the HIV-1 infection, plasma factors produced in response to the infection, but not the virus itself, perturb DC function. Apoptotic microparticles (MPs), small membraneous blebs derived from dying white blood cells during AHI, can inhibit DCs through the phagocytic glycoprotein CD44. He is currently unraveling the cellular and molecular pathways by which DCs are dysregulated through apoptotic MPs, both in AHI and in other disease settings that result in such apoptotic debris.

Davor Frleta, PhD. Senior Scientist

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