Quantitative proteomic analysis of human monocyte-derived dendritic cells after exposure to live Brugia malayi microfilariae

摘要

Brugia malayi (Bm) is one of three filarial species (Wuchereria bancrofti, Bm, and Brugia timori) that causes lymphatic filariasis (LF). Although it is the second leading cause of permanent disability in the world, the pathogenesis of LF is still not well understood. Bm goes through a complicated life cycle that involves mammalian hosts and insect vectors. The infective larvae (L3) are transmitted by mosquito to human and develop into adults in the lymphatic system. Microfilariae (MF) are then released by adult worms into blood stream and potentially mediate many of the immunologic defects associated with chronic lymphatic filariasis. Dendritic cells (DC) are professional antigen presenting cells that play pivotal roles in both innate and adaptive immune responses. Furthermore, it has been shown that live MF of Brugia malayi modulates dendritic cell function by two different mechanisms: 1) by altering TLR3 and TLR4 expression and function; and 2) by inducing apoptotic DC cell death [1, 2]. Most studies to date on the subject have been limited to transcriptome analysis using microarrays. Therefore, an extensive quantitative proteomic analysis of DC cells after exposure to live Bm MF should provide us with new insights into the effects and mechanisms of MF on the host immune response at the protein level.