Preexposure to Live Brugia malayi Microfilariae Alters the Innate Response of Human Dendritic Cells to Mycobacterium tuberculosis.

摘要

Background. Mycobacterium tuberculosis and helminth coinfection is highly prevalent, and the presence of helminths may modulate the Th1 response necessary for M. tuberculosis control.Methods. Elutriated human monocytes, differentiated into dendritic cells (DCs) and macrophages, were exposed in vitro to live microfilariae (mf). The influence that mf had on M. tuberculosis infectivity, expression of cell surface molecules, and production of cytokines was determined.Results. Compared with mf-unexposed, M. tuberculosis-infected cells, mf-exposed, M. tuberculosis-infected DCs had decreased expression of CD14, CD54, and human leukocyte antigen-DR, and mf-exposed, M. tuberculosis-infected macrophages had decreased expression of CD40. DCs that were mf exposed and M. tuberculosis infected produced more interleukin (IL)-1 beta than did mf-unexposed, M. tuberculosis-infected DCs. Also, mf-exposed, M. tuberculosis-infected DCs and macrophages expressed less IL-10 and interferon (IFN)- alpha than did mf-unexposed, M. tuberculosis-infected cells. When they were cultured with autologous CD4(+) T cells, mf-exposed, M. tuberculosis-infected DCs were less capable of stimulating the production of IFN- gamma than were other DCs. Exposure of DCs to mf decreased the surface expression of DC-specific intercellular adhesion molecule-3 grabbing nonintegrin, a receptor required by M. tuberculosis for entry into DCs.Conclusions. Exposure to mf reduces a key receptor on the DC surface, which perhaps renders these cells less susceptible to infection with M. tuberculosis. Exposure to mf changes the surface expression of adhesion and costimulatory molecules on DCs and macrophages and alters their expression of cytokines and chemokines in a way that renders them less capable of immunologic responses.