Curtailment of Toll-like receptor signalling and cytokine production in dendritic cells by secreted products of Heligmosomoides polygyrus

Many successful pathogens have evolved to release molecular products that can manipulate DC responses to dampen immunity. Here, we report that the excretory/secretory (ES) products of the intestinal helminth Heligmosomoides polygyrus bakeri profoundly repress the ability of murine bone marrow derived DCs to respond to canonical stimuli delivered through Toll-like Receptors (TLRs), e.g. LPS.

To further investigate the effect of HES on GMDC activation in response to LPS, we compared gene-expression profiles of LPS-treated and LPS+HES-treated cells. It was noted that HES broadly reduced the transcript levels of activation markers such as costimulatory molecules (e.g. CD40 and CD83) and pro-inflammatory cytokines (e.g. IL-12p35, LT-α and IL-23p19), and even some TLRs (e.g. TLR1 and TLR6). On the other hand, HES-treatment increased the expression of type-2 markers such as IL-33 and arginase 1, and transcripts of genes involved in cellular metabolism (e.g. HIF1A, Hmox, and Txnip).