Brugia malayi filarial helminth-derived extracellular vesicles suppress antigen presenting cell functions and antigen-specific CD4+ T cell responses

Live microfilariae (Mf) and mf-derived extracellular vesicles (EVs) have been shown to modulate human antigen presenting cell (APC) function, most notably by suppressing the induction of IL-12 (and other pro-inflammatory cytokines) following activation with LPS and interferon-gamma. To explore further how EVs alter human APC function, we studied the effect of mf and EVs on human elutriated monocyte-derived DCs following exposure to Mf, Mf-derived excretrory/secretory (E/S) products, E/S depleted of EVs through ultracentrifugation and purified EVs using RNAseq analysis. In our analyses of the data for the DC, using a false discovery rate (FDR)<0.05, EV-exposed DCs had induced the expression of 212 differentially expressed genes (DEGs) when compared to unexposed DC and 157 when compared to ES-depleted EVs. These genes were enriched in GO biological processes associated with neutrophil degranulation and 15 DEGs associated with KEGG Lysosome pathways. IPA analysis point to immune dysregulation. Overall design: We performed comparative RNAseq analysis of human DC following exposure to live Brugia malayi filarial helminth, EVs, E/S, or EV-depleted E/S.