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Identification of intracellular signaling pathways activated in ESP-treated dendritic cells.


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Zarrabian, Bahar; Tam, Mifong; Valanparambil, Rajesh; Geary, Timothy et Stevenson, Mary M . Identification of intracellular signaling pathways activated in ESP-treated dendritic cells. In: 12ième Symposium Annuel de Parasitologie Moléculaire du Québec, 28-29 mai 2012, INRS- Institut Armand-Frapper, Laval, Qc, Canada.

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The murine nematode Heligmosomoides po/ygyrus serves as a madel for studying human gastrointestinal helminth infections, which are highly endemie in areas of poor sanitation worldwide. H. po/ygyrus is recognized for its patent modulatory effects on host immune responses to unrelated antigens. Excretorysecretory products (ESP) released from adult H. polygyrus worms have been shawn ta be responsible for the immunosuppressive effects. Our previous studies showed that H. polygyrus-derived ESP modulates immune responses to unrelated antigens by inhibiting dendritic cell (DC) maturation and cytokine production in response to patent TLR ligands, but the intracellular signaling pathway(s) by which ESP modulates DC function are unknown. To identify the signaling pathways involved, bane marrow-derived dendritic cells (BMDC) were stimulated in vitro with medium, CpG-ODN, ESP, or ESP prior to CpG-ODN. Following overnight culture, BMDC lysates were prepared and analyzed by Western blotting for differentiai signaling cascades, namely, the MAPK and spleen tyrosine kinase (Syk) pathways. Neither p38 MAPK, Erk 1/2, nor pSAPK/JNK were differentially regulated as a result of DC stimulation with ESP. However, we observed increased PL C-yl expression, indicating activation of the Syk pathway known to be involved in response to C-type lectins. Collectively, our data suggest that DC may recognize ESP in a TLRindependent manner but that H. polygyrus-derived ESP may induce signaling in DC via the Syk pathway. ln conclusion, these observations provide novel information that may be useful in identifying H. polygyrusderived ESP proteins involved in modulating DC function.

Type de document: Document issu d'une conférence ou d'un atelier
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 05 juill. 2017 20:24
Dernière modification: 05 juill. 2017 20:24
URI: https://espace.inrs.ca/id/eprint/5683

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