Helminth regulation of host IL-4R[alpha]/Stat6 signaling: Mechanism underlying NOS-2 inhibition by Trichinella spiralis

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-4R[alpha])/Stat6-dependent but T cell-independent pathway is the key for the nematodeinduced host NOS-2 inhibition; (ii) endogenous IL-4 and IL-13, the only known IL- 4R[alpha] 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. inflammation I nematode | immunoregulation | nitric oxide | endotoxin