Reactive Nitrogen and Oxygen Species Ameliorate Experimental Cryptosporidiosis in the Neonatal BALB/c Mouse Model

Leitch, Gordon J.; He, Qing

doi:10.1128/iai.67.11.5885-5891.1999

Cited by 51 publications

(28 citation statements)

References 59 publications

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“…1C). Consistent with results from previous studies (14,28), the upregulation of inflammatory genes, such as those for colony-stimulating factor 2 (Csf2), inducible nitric oxide synthase 2 (Nos2), interleukin 10 (Il-10), and C-X-C motif chemokine ligand 2 (Cxcl2), in the intestinal epithelium of infected animals compared with their expression in the intestinal epithelium of the noninfected control mice was detected ( Fig. 1D).…”

Section: Resultssupporting

confidence: 90%

Induction of Inflammatory Responses in Splenocytes by Exosomes Released from Intestinal Epithelial Cells followingCryptosporidium parvumInfection

et al. 2019

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Cryptosporidium, a protozoan parasite that infects the gastrointestinal epithelium and other mucosal surfaces in humans and animals, is an important opportunistic pathogen in AIDS patients and one of the most common enteric pathogens affecting young children in developing regions. This parasite is referred to as a “minimally invasive” mucosal pathogen, and epithelial cells play a central role in activating and orchestrating host immune responses. We previously demonstrated that Cryptosporidium parvum infection stimulates host epithelial cells to release exosomes, and these released exosomes shuttle several antimicrobial peptides to carry out anti-C. parvum activity. In this study, we detected the upregulation of inflammatory genes in the liver and spleen following C. parvum intestinal infection in neonatal mice. Interestingly, exosomes released from intestinal epithelial cells following C. parvum infection could activate the nuclear factor kappa B signaling pathway and trigger inflammatory gene transcription in isolated primary splenocytes. Several epithelial cell-derived proteins and a subset of parasite RNAs were detected in the exosomes released from C. parvum-infected intestinal epithelial cells. Shuttling of these effector molecules, including the high mobility group box 1 protein, was involved in the induction of inflammatory responses in splenocytes induced by the exosomes released from infected cells. Our data indicate that exosomes released from intestinal epithelial cells upon C. parvum infection can activate immune cells by shuttling various effector molecules, a process that may be relevant to host systemic responses to Cryptosporidium infection.

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Section: Resultssupporting

confidence: 90%

Induction of Inflammatory Responses in Splenocytes by Exosomes Released from Intestinal Epithelial Cells followingCryptosporidium parvumInfection

et al. 2019

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“…Reduction and elimination of shedding oocyst in response to the treatments might be attributable to a direct effect on parasite growth in the intestines, the production of the sexual phases, and/ or the formation of oocysts. The present histopathological changes in the infected/untreated group ileum tissues were reported (Tzipori et al, 1994;Capet et al, 1999;Leitch and He, 1999;Motta et al, 2002;Guitard et al, 2006;Maruyama et al, 2007;Robinson and Smyth, 2008). Pathological changes were attributed to C. parvum displacing brush borders causing an asymmetrical loss of epithelial cells resulting in shortening and fusing of villi.…”

Section: Proved This Immunologicallymentioning

confidence: 56%

The Efficacy of Three Medicinal Plants ; Garlic , Ginger and Mirazid and a Chemical Drug Metronidazole against Cryptosporidium Parvum : Ii- Histological Changes

Abouel-Nour¹,

El-Shewehy²,

HAMADA³

2016

JESP

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Cryptosporidiosis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells of man and animals causing a major health problem. This study was oriented to evaluate the protective and curative capacity of garlic, ginger and mirazid in comparison with metronidazole drug (commercially known) against Cryptosporidium in experimental mice. Male Swiss Albino mice experimentally infected with C. parvum were treated with medicinal plants extracts (Ginger, Mirazid, and Garlic) as compared to chemical drug Metronidazole. Importantly, C. parvum-infected mice treated with ginger, Mirazid, garlic and metronidazole showed a complete elimination in shedding oocysts by 9 th day PI. The reduction and elimination of shedding oocysts in response to the treatments might be attributable to a direct effect on parasite growth in intestines, sexual phases production and/ or the formation of oocysts. The results were evaluated histopathological examination of ileum section of control mice (uninfected, untreated) displayed normal architecture of the villi. Examination of infected mice ileum section (infected, untreated) displayed histopathological alterations from uninfected groups. Examination of ileum section prepared from mice treated with garlic, ginger, mirazid, and metronidazole displayed histopathological alterations from that of the control groups, and showed marked histologic correction in the pattern with the four regimes used in comparison to control mice. Garlic successfully eradicated oocysts of infected mice from stool and intestine. Supplementation of ginger to infected mice markedly corrected elevation in the inflammatory risk factors and implied its potential antioxidant, anti-inflammatory and immunomodulatory capabilities. Infected mice treated with ginger, mirazid, garlic and metronidazole showed significant symptomatic improvements during treatment.

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“…Results of the present study demonstrate that C. parvum infection leads to induction of iNOS and increased synthesis of NO and PGE 2 by parasitized intestinal mucosa. Studies in mice have shown that C. parvum infection is associated with an increase in iNOS expression by the epithelium (31). Although we did not specifically investigate the long-term consequences of iNOS expression in C. parvum infection, prior observations have shown that exposure to high concentrations of NO promotes cytotoxicity and permeability of cultured epithelia (7,34,41,43,46).…”

Section: Discussionmentioning

confidence: 96%

“…These observations suggest a role for iNOS in purging the intestine of the infection. More specifically, NO donors have been shown in vitro to reduce viability of C. parvum sporozoites (30), and iNOS knockout mice or mice treated with NOS inhibitors have more severe intestinal infection and delayed parasite clearance (30,31). Nevertheless, the Fig.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide synthase stimulates prostaglandin synthesis and barrier function inC. parvum-infected porcine ileum

Gookin¹,

Duckett²,

Armstrong³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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Cell culture models implicate increased nitric oxide (NO) synthesis as a cause of mucosal hyperpermeability in intestinal epithelial infection. NO may also mediate a multitude of subepithelial events, including activation of cyclooxygenases. We examined whether NO promotes barrier function via prostaglandin synthesis using Cryptosporidium parvum-infected ileal epithelium in residence with an intact submucosa. Expression of NO synthase (NOS) isoforms was examined by real-time RT-PCR of ileal mucosa from control and C. parvum-infected piglets. The isoforms mediating and mechanism of NO action on barrier function were assessed by measuring transepithelial resistance (TER) and eicosanoid synthesis by ileal mucosa mounted in Ussing chambers in the presence of selective and nonselective NOS inhibitors and after rescue with exogenous prostaglandins. C. parvum infection results in induction of mucosal inducible NOS (iNOS), increased synthesis of NO and PGE2, and increased mucosal permeability. Nonselective inhibition of NOS (NG-nitro-L-arginine methyl ester) inhibited prostaglandin synthesis, resulting in further increases in paracellular permeability. Baseline permeability was restored in the absence of NO by exogenous PGE2. Selective inhibition of iNOS [L-N6-(1-iminoethyl)-L-lysine] accounted for approximately 50% of NOS-dependent PGE2 synthesis and TER. Using an entire intestinal mucosa, we have demonstrated for the first time that NO serves as a proximal mediator of PGE2 synthesis and barrier function in C. parvum infection. Expression of iNOS by infected mucosa was without detriment to overall barrier function and may serve to promote clearance of infected enterocytes.

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Reactive Nitrogen and Oxygen Species Ameliorate Experimental Cryptosporidiosis in the Neonatal BALB/c Mouse Model

Cited by 51 publications

References 59 publications

Induction of Inflammatory Responses in Splenocytes by Exosomes Released from Intestinal Epithelial Cells followingCryptosporidium parvumInfection

Induction of Inflammatory Responses in Splenocytes by Exosomes Released from Intestinal Epithelial Cells followingCryptosporidium parvumInfection

The Efficacy of Three Medicinal Plants ; Garlic , Ginger and Mirazid and a Chemical Drug Metronidazole against Cryptosporidium Parvum : Ii- Histological Changes

Nitric oxide synthase stimulates prostaglandin synthesis and barrier function inC. parvum-infected porcine ileum

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