A Type I IFN-Dependent Pathway Induced by Schistosoma mansoni Eggs in Mouse Myeloid Dendritic Cells Generates an Inflammatory Signature

Abstract

Schistosomes are helminth parasites that display a dual impact on the immune system of their hosts. Although the larval stage, also known as schistosomulum, appears to subvert the host defenses, the egg stage induces strong inflammatory reactions. Given the pivotal role of dendritic cells (DC) in initiating and regulating immune responses, we compared the distinct transcriptional programs induced in immature mouse DC by S. mansoni eggs or schistosomula. Although SLA abrogated the transcription of many genes implicated in DC functions, eggs caused myeloid DC to produce IFN-β. Autocrine/paracrine signaling through the type I IFN receptor in response to eggs was necessary for the induction of known IFN-responsive genes and enhanced the synthesis of key inflammatory products. Taken as a whole, our data provide molecular insights into the immune evasion mechanism of schistosomula and suggest an unexpected role for type I IFN in the innate response to helminth eggs.

Double-stranded RNAs from the Helminth Parasite Schistosoma Activate TLR3 in Dendritic Cells

“…Although until now the effects of live eggs on TLR activation have not been investigated, two independent studies have shown the implication of TLR2 and TLR4 in the recognition of certain egg components (17,18). Recently, using a genome-wide expression study, we found that live eggs induce a transcriptional program in myeloid DCs that culminates in the production of many IFN-induced inflammatory gene products (16). In the present study, we have taken a genetic and molecular approach to identify the TLR members involved in this phenomenon.…”

“…Using high density oligonucleotide microarrays, we have recently demonstrated that the egg stage of the metazoan parasite Schistosoma mansoni activates the transcription of many genes in myeloid DCs including those encoding cell surface markers (CD40 and CD86), inflammatory (TNF-␣), and immunoregulatory (IL-12p40) cytokines as well as ISGs (16). This signature is highly evocative of a TLR dependence.…”

“…The kinetic global gene expression analysis of mouse DCs suggested that S. mansoni live eggs activate DCs through TLR engagement (16). We first aimed to analyze the contribution of MyD88, a critical adaptor molecule used by all TLRs (with the exception of TLR3) (27,28) in the egg-induced DC activation.…”

Activation of Invariant NKT Cells by the Helminth Parasite Schistosoma mansoni

“…Activation of TLRs by pathogens is the main pathway by which DCs become activated (42)(43)(44). We have shown recently that schistosome eggs activate DCs in vitro to mature and to produce immunostimulatory factors, including IL-12, via TLR2 and TLR3 (38,45). To check the potential involvement of these TLRs, WT, TLR2, TLR3, or double TLR2/TLR3-deficient DCs were sensitized with live eggs, and their ability to activate LMCs in vitro was then assessed.…”

Targeting molecular signaling pathways of Schistosoma haemotobium infection in bladder cancer

“…Carcinoma of the bladder is a long-term sequela of chronic infection. 21,[31][32][33] Bladder cancer is one of the most severe complications of chronic schistosomiasis. Case report studies indicate that individuals with schistosomiasis may develop bladder cancer earlier than uninfected people.…”