Nitric Oxide Mediates Intestinal Pathology But Not Immune Expulsion DuringTrichinella spiralisInfection in Mice

Abstract

The relationship between intestinal pathology and immune expulsion of gastrointestinal (GI) nematodes remains controversial. Although immune expulsion of GI helminth parasites is usually associated with Th2 responses, the effector mechanisms directly responsible for parasite loss have not been identified. We have previously shown that while the intestinal pathology accompanying the expulsion of the GI parasite Trichinella spiralis may be dependent on IL-4 and mediated by TNF, parasite loss is independent of TNF. In contrast, intestinal pathology in other disease models has been attributed to Th1 cytokines, although it closely resembles that seen in helminth infections. Whereas production of inducible NO synthase (iNOS) in the gut is important for both homeostasis of the epithelial layer and in protection against pathogenic microorganisms, overproduction of NO has been implicated in the pathogenesis of a number of inflammatory conditions. We therefore investigated the role of NO in T. spiralis infection using iNOS-deficient mice. iNOS−/− and iNOS-/+ mice were infected with T. spiralis, and parasite expulsion and intestinal pathology were followed. Parasite expulsion proceeded similarly in both groups of animals, but significant intestinal pathology was only observed in the heterozygous mice. Thus it appears that, although the protective effects of Th2 responses in GI helminth infection do not require NO, this mediator contributes substantially to the associated enteropathy. NO may therefore be an important mediator of enteropathy in both Th1- and Th2-inducing conditions.

Counter-Protective Role for Interleukin-5 during AcuteToxoplasma gondiiInfection

“…Thus, treating such mice systemically with aminoguanidine reduced intestinal NO production and increased survival. However, it has recently been demonstrated in Trichnella spiralis infections that Th2-dependent responses can also mediate enteropathology and, moreover, that this is also through NO production as a consequence of IL-4-mediated TNF-␣ production (19,20). Thus as IL-5 can promote IL-4 production and a Th2 response and eosinophils themselves are potent NO producers, we examined the role of NO in IL-5Ϫ/Ϫ and WT mice infected orally with T. gondii.…”

The mucosal cellular response to infection withAncylostoma ceylanicum

“…In mice infected with T. spiralis and other intestinal nematodes their numbers increase within a few days of infection, and then decline once the worms have been eliminated (Kamal et al, 2001(Kamal et al, , 2002Elphick & Mahida, 2005). Collectively, these cellular changes are accompanied by gross changes of the mucosal architecture, reflected in a reduction of the size of villi and hyperplasia in the crypts (Garside et al, 1992;Lawrence et al, 2000) Hookworm infections, which give rise to chronic infections in humans and animals (Behnke, 1987) are known also to stimulate intestinal inflammatory responses, probably the earliest evidence for this going back to Whipple (1909). They also have a marked effect on intestinal morphology, which has been attributed both to the biting activities of adult worms and to the accompanying host response (Alkazmi et al, 2006).…”

Acute and persisting Th2-like immune response after fractionated colorectal γ-irradiation

“…Furthermore, the maturation stage of the macrophage population may be worth considering in the later phase. The immunomodulatory activity of iNOS is reported to influence Th cell development and to downregulate the induction of Th1 responses, thereby promoting a Th2 response [30] . Multiple pathways appear to be involved in initiating the type 2 T-cell responses.…”