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. We performed comparative RNAseq analysis of human DC following exposure to live Brugia malayi filarial helminth, EVs, E/S, or EV-depleted E/S.