Open AccessHelminth regulation of host IL-4Rα/Stat6 signaling: Mechanism underlying NOS-2 inhibition byTrichinella spiralis
Author(s) -
Ka Bian,
Meng Zhong,
Yael Harari,
Mildred Lai,
Norman W. Weisbrodt,
Ferid Murad
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0409461102
Subject(s) - trichinella spiralis , biology , stat6 , nitric oxide synthase , microbiology and biotechnology , host (biology) , signal transduction , immune system , receptor , nematode , protein subunit , immunology , nitric oxide , interleukin 4 , helminths , biochemistry , endocrinology , gene , ecology
Gastrointestinal nematode infection is known to alter host T cell activation and has been used to study immune and inflammatory reactions in which nitric oxide (NO) is a versatile player. We previously demonstrated that Trichinella spiralis infection inhibits host inducible NO synthase (NOS-2) expression. We now demonstrate that (i) an IL-4 receptor alpha-subunit (IL-4Ralpha)/Stat6-dependent but T cell-independent pathway is the key for the nematode-induced host NOS-2 inhibition; (ii) endogenous IL-4 and IL-13, the only known IL-4Ralpha ligands, are not required for activating the pathway; and (iii) treatment of RAW264.7 cells with parasite-cultured medium inhibits NOS-2 expression but not cyclooxygenase 2 expression. We propose that a yet-unidentified substance is released by the nematode during the host-parasite interaction.