Contrasting roles for IL‐10 in protective immunity to different life cycle stages of intestinal nematode parasites

Abstract

Expulsion of the gastro‐intestinal nematode Trichinella spiralis is associated with a pronounced mastocytosis mediated by a T helper (Th) 2 type response involving interleukin (IL)‐4 and IL‐13. Here we demonstrate that IL‐10 is a key regulator of protective immune responses against T. spiralis in vivo. IL‐10 knockout mice or normal mice treated with a neutralizing anti‐IL‐10 receptor antibody are highly susceptible to a primary T. spiralis infection and show significantly delayed adult worm expulsion. Depletion of IL‐10 resulted in elevated Th1 and Th2 cytokine responses but significantly reduced numbers of mucosal mast cells in the jejunum. Interestingly, the increase in IFN‐γ detected in the absence of IL‐10 resulted in increased immunity to larval stages. Hence, IL‐10 has a negative effect on immunity to the tissue dwelling larval stages of T. spiralis but plays a significant biological role as an in vivo regulator of intestinal mast cell responses and is crucially involved in protection against adult stages of intestinal parasites in vivo.

Th2 induction by Nippostrongylus secreted antigens in mice deficient in B cells, eosinophils or MHC Class I-related receptors

“…This implies that IL-10 release may not simply be a consequence of Th2 expansion, but may be required to initiate Th2 responses to helminths. This is exactly the conclusion proposed from studies on Trichuris muris and Trichinella spiralis, in which IL-10 deficiency abolishes the capacity of mice to mount a protective Th2 response [35,36]. Future studies with IL-10 gene-targetted animals could explore not only the relationship between nematode infection and Th2 generation, but also the possible involvement of IL-10 in down-regulatory interactions in chronic helminth infection [37].…”

Development of cellular immune response of mice to infection with low doses of Trichinella spiralis, Trichinella britovi and Trichinella pseudospiralis larvae

“…(Frydas et al 1996, Dzik et al 2002. IFN-γ is crucially involved in protection against newborn larvae, but does not affect the expulsion of adult worms (Helmby and Grencis 2003). Its increased production confirms its participation in immune response at the muscle phase.…”

“…IFN-γ inhibits macrophage secretion of IL-10 (Mosmann 1994). The balance between IL-10 and IFN-γ determines the development of immunity against the life stages of the parasite (Helmby and Grencis 2003). Beiting et al (2004) revealed a role for IL-10 in limiting inflammatory responses during the early stages of muscle infection by T. spiralis, but the chronic inflammation is independent on IL-10 and is accompanied by a shift to a Th2 response following completion of parasite development in the muscle.…”

Removal of Regulatory T Cell Activity Reverses Hyporesponsiveness and Leads to Filarial Parasite Clearance In Vivo

“…In the immune response to S. mansoni infection, which contains both Th1 and Th2 components, IL-10 production by CD4 ϩ CD25 ϩ Tregs is linked to the inhibition of Th1 immunity and subsequent augmentation of Th2 (28, 32). Similarly, differential effects of IL-10 on Th1 and Th2 responses have been noted during infection with Trichinella spiralis, where IL-10 deficiency has been found to inhibit Th2-mediated killing of the adult worms, while simultaneously promoting the Th1-mediated killing of muscle larvae (75). We conclude that although IL-10 does dampen Th1 immunity during L. sigmodontis infection, it does not play a key role in promoting parasite survival in the largely Th2-dependent context of immunity to L. sigmodontis.…”