Kinetics of mucosal ileal gamma-interferon response during cryptosporidiosis in immunocompetent neonatal mice

Kapel, Nathalie; Benhamou, Yves; Buraud, M.; Magne, Denis; Opolon, P; Gobert, J.G.

doi:10.1007/s004360050182

Cited by 42 publications

(38 citation statements)

References 14 publications

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“…Furthermore, it is noteworthy that prolonged exposure to IFNc down-regulates Na + -coupled glucose absorption in T84 cells (Yoo et al 2000) and the activity of brush-border membrane Na + /H + exchangers (NHE2, NHE3) in Caco-2 cells and rat intestine (Rocha et al 2001). Such a mucosal secretion of IFNc is known to occur during experimental cryptosporidiosis in our model, its kinetics being similar to those of oocyst excretion (Kapel et al 1996). We can therefore hypothesize that the intestinal absorption of all essential and non-essential amino acids transported through a Na + -dependent pathway may be downregulated during acute cryptosporidiosis.…”

Section: Discussionmentioning

confidence: 57%

Evidence for the absence of an intestinal adaptive mechanism to compensate for C. parvum -induced amino acid malabsorption in suckling rats

Topouchian

Huneau

Barbot

et al. 2003

Parasitology Research

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In order to assess the impact of Cryptosporidium parvum on host intestinal physiology, we investigated absorption of the two principal amino acids in dam's milk (leucine, glutamate), using Ussing chambers and RT-PCR analyses. Experiments were performed in both heavily (ileum) and mildly (duodenum) infected segments of the small intestine at the peak of infection [day 8 post-infection (PI)] and after spontaneous clearance of the parasite (day 17 PI). At day 8 PI, amino acid fluxes across the mucosa were decreased throughout the small intestine (P<0.01) and EAAT3 mRNA expression was reduced ( from -49% to -28%). At day 17 PI, leucine and glutamate fluxes were normalized but the decrease in EAAT3 mRNA levels persisted (from -31% to -46%). Our results demonstrate that cryptosporidiosis induces major amino acid malabsorption involving the entire small intestine which is not counterbalanced by any up-regulation, even after spontaneous clearance of the parasite.

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Section: Discussionmentioning

confidence: 57%

Evidence for the absence of an intestinal adaptive mechanism to compensate for C. parvum -induced amino acid malabsorption in suckling rats

Topouchian

Huneau

Barbot

et al. 2003

Parasitology Research

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“…It had previously been shown that IFN-␥ expression was increased in the terminal ileum as early as 3 days after C. parvum infection (14). Earlier expression of IFN-␥, well prior to the onset of adaptive immunity, has not been reported.…”

Section: Resistance To and Control Of Cryptosporidium Parvum Infectiomentioning

confidence: 96%

An Early Intestinal Mucosal Source of Gamma Interferon Is Associated with Resistance to and Control ofCryptosporidium parvumInfection in Mice

et al. 2005

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Resistance to and control of Cryptosporidium parvum infection in mice in the absence of adaptive immunity appears to be gamma interferon (IFN-␥) dependent. Using an IFN-␥-neutralizing antibody in a murine model, we demonstrated increased susceptibility to infection within 24 h. We correlated this early resistance and control with increased mucosal expression of IFN-␥ and demonstrate that CD8 ؉ T-cell receptor ␣␤ intestinal intraepithelial lymphocytes express and secrete this cytokine shortly after infection. The rapid kinetics of IFN-␥ expression and secretion by naive CD8 ؉ T cells in response to a protozoan pathogen have not previously been demonstrated.Cryptosporidium parvum is an enteric, intracellular, zoonotic parasite that causes significant morbidity, particularly among people suffering from AIDS and children in developing countries. With the exception of highly active antiretroviral therapy, there remains no effective therapy for AIDS-related cryptosporidiosis. Our understanding of the immune response to C. parvum is not complete. From studies of human and animal cryptosporidiosis, it is apparent that adaptive immunity, in the form of CD4 ϩ T cells and the cytokine gamma interferon (IFN-␥), is important for resistance to and clearance of the infection (24). However, there is convincing evidence from studies of C. parvum infection in scid mice of an IFN-␥-dependent innate resistance to infection with this parasite (7). The mechanism of this innate immune response as well as the source of IFN-␥ in this setting, however, remains undefined. Since C. parvum infects primarily the gastrointestinal epithelium, we hypothesized that immune cells within the mucosa contribute to this innate IFN-␥-dependent immunity.The purpose of this study was to demonstrate the presence of and characterize the IFN-␥-dependent innate immune response to C. parvum infection in mice. We hypothesized that intraepithelial lymphocytes (iIEL) are mediators of this IFN-␥-dependent innate immunity. Using a neutralizing anti-IFN-␥ antibody, we show increased susceptibility to C. parvum infection in C57BL/6 wild-type mice within 24 h after infection. We also demonstrate increased IFN-␥ expression within the terminal ileum in mice 24 h after infection with C. parvum and identify the specific cellular compartments that contribute to this early cytokine expression.Early resistance to C. parvum infection is IFN-␥ dependent.

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“…Mucosal immune response, especially IFNγ secretion, is known to play a key role in resistance to C. parvum infection (Ungar et al 1991;Chen et al 1993;Kapel et al 1996;You and Mead 1998). A type 2 response involving IL4 and IL10 has been more recently related to parasite clearance (Lacroix et al 2001).…”

Section: Introductionmentioning

confidence: 97%

Experimental study of the effects of probiotics on Cryptosporidium parvum infection in neonatal rats

Guitard¹,

Menotti

Desveaux

et al. 2006

Parasitol Res

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To date, there is no efficient treatment for cryptosporidiosis and parasite eradication relies on innate and acquired immunity. In this study, we investigated the effect of administration of probiotic bacteria on the development and progression of the experimental infection in suckling rats. Rats were fed daily with 2.10(7) CFU of Lactobacillus casei-containing mixture, starting 2 days before the infection until the spontaneous clearance of the parasite. Effects on weight gain, parasite burden, mucosal histology and production of mucosal cytokines (IFNgamma, IL10 and TNFalpha) were studied. Although a trend to a more rapid clearance of parasites was noted in rats treated with probiotics, no significant effect of probiotics administration was observed in terms of weight gain, parasite burden, mucosal damage, or kinetics of mucosal cytokines during the course of infection. Overall, our results showed that the daily administration of L. casei-containing mixtures was unable to eradicate the parasite in our model.

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Kinetics of mucosal ileal gamma-interferon response during cryptosporidiosis in immunocompetent neonatal mice

Cited by 42 publications

References 14 publications

Evidence for the absence of an intestinal adaptive mechanism to compensate for C. parvum -induced amino acid malabsorption in suckling rats

Evidence for the absence of an intestinal adaptive mechanism to compensate for C. parvum -induced amino acid malabsorption in suckling rats

An Early Intestinal Mucosal Source of Gamma Interferon Is Associated with Resistance to and Control ofCryptosporidium parvumInfection in Mice

Experimental study of the effects of probiotics on Cryptosporidium parvum infection in neonatal rats

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