Intestinal Inflammation-Mediated Clearance of Amebic Parasites Is Dependent on IFN-γ

Abstract

Intestinal amebiasis is a major cause of diarrhea. However, research on host-amebae interactions has been hampered owing to a lack of appropriate animal models. Recently, a mouse model of intestinal amebiasis was established, and using it, we reported that colonized the intestine in a manner similar to that of the pathogenic In this study, we evaluated the protective mechanisms present against amebae using this model. CBA/J mice infected with had a persistent infection without apparent symptoms. In contrast,infected mice rapidly expelled the ameba, which was associated with weight loss, diarrhea, and intestinal damage characterized by apoptosis of intestinal epithelial cells (IECs). Expression of NKG2D on intestinal intraepithelial lymphocytes (IELs) and IFN-γ-producing cells in Peyer's patches were significantly induced after infection with but not with IFN-γ-deficient mice infected with showed no obvious symptoms. Notably, none of these mice expelled, indicating that IFN-γ is responsible not only for intestinal symptoms but also for the expulsion of amebae. Furthermore, apoptosis of IECs and expression of NKG2D on IELs observed in infected mice did not occur in the absence of IFN-γ. In vivo blocking of NKG2D in mice infected with enabled ameba to survive longer and remarkably reduced apoptotic IECs. Our results clearly demonstrate a novel protective mechanism exerted by IFN-γ against intestinal amebae, including induction of cytotoxicity of IELs toward IECs.

Mechanisms of activation of innate-like intraepithelial T lymphocytes

“…55 Although NKG2D is not expressed at the surface of murine intestinal T-IEL in normal conditions, cytokine-dependent NKG2D upregulation has been observed during infections. Hence, IL-15 mediates NKG2D expression on CD8αα T-IEL following poly(I:C) treatment in vivo, 58 infection with Entamoeba moshkovskii triggers IFNγ production which is required for NKG2D expression on TCRαβ CD8αα T-IEL, 59 and increased IL-1β production regulates γδ T-IEL NKG2D expression following Salmonella typhimurium infection in TLR9 −/− mice. 60 Of note, in addition to upregulating NKG2D expression, these cytokines also facilitated NKG2D ligand expression on epithelial cells.…”

“…60 Of note, in addition to upregulating NKG2D expression, these cytokines also facilitated NKG2D ligand expression on epithelial cells. 59,60 NKG2D engagement triggers cytotoxicity of NK cells and T-IEL. Human intestinal CD8αβ T-IEL spontaneously kill selected colon cancer cell lines that express even low levels of NKG2D ligands, by triggering FasL-mediated cytotoxicity.…”

“…55 Although human intestinal induced T-IEL constitutively express NKG2D, its expression can be further upregulated by IL-15. 55 In coeliac disease, NKG2D-mediated IEL cytotoxicity is thought to be In vitro killing assay 55,57,61 Poly(I:C) treatment 58 Salmonella and E. moshkovskii infection 59,60 Coeliac disease [62][63][64] Inhibitory (NKG2A dimerization) Costimulatory (NKG2C or E/H dimerization)…”

“… 60 Of note, in addition to upregulating NKG2D expression, these cytokines also facilitated NKG2D ligand expression on epithelial cells. 59 , 60 …”

Escherichia coli mediated resistance of Entamoeba histolytica to oxidative stress is triggered by oxaloacetate

“…The effect of oxaloacetate on the survival of E . histolytica in the large intestine was tested in a mouse strain resistant to intestinal amebiasis C57BL/6 (B6) [ 50 ] and in a mouse strain susceptible to intestinal amebiasis CBA/J [ 51 ]. The survival of the parasite was determined by counting the number of trophozoites in the stool after cultivation and by amplification of E .…”