Human Intestinal Epithelial Cells Respond toCryptosporidium parvumInfection with Increased Prostaglandin H Synthase 2 Expression and Prostaglandin E2and F2αProduction

Laurent, Fabrice; Kagnoff, Martin F.; Savidge, Tor; Naciri, Muriel; Eckmann, Lars

doi:10.1128/iai.66.4.1787-1790.1998

Cited by 85 publications

(42 citation statements)

References 24 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human intestinal xenografts were generated as described before. 6,[32][33][34][35][36] Briefly, human fetal intestine, gestational age 16-20 weeks (Advanced Biosciences Resources, Alameda, CA) was transplanted subcutaneously onto the backs of C57BL ⁄6 SCID mice. Intestinal xenografts were allowed to mature for at least 10 weeks after transplantation, at which time the epithelium, which is strictly of human origin, is fully differentiated.…”

Section: Human Intestinal Xenograftsmentioning

confidence: 99%

Expression of Epstein–Barr virus‐induced gene 3 and other interleukin‐12‐related molecules by human intestinal epithelium

et al. 2004

Self Cite

View full text Add to dashboard Cite

SUMMARYAntigen-presenting cells, including dendritic cells, monocytes and macrophages, produce members of the interleukin-12 (IL-12) family that are important in initiating and maintaining cell-mediated immune responses. These include IL-12p35 and p19 that dimerize with IL-12p40 to form IL-12 (also termed IL-12p75) and IL-23, respectively, and Epstein-Barr virus-induced gene 3 (EBI3) protein (a protein related to IL-12p40), that forms a dimer with p28, termed IL-27. Intestinal epithelial cells, which are the initial site of contact between the host and enteric pathogens, can act as antigen-presenting cells, and are known to express mediators important in inflammatory and immune responses. In the current studies, we hypothesized that intestinal epithelial cells express members of the IL-12 family, which can function as an early signalling system important in mucosal immunity. Using in vitro and in vivo model systems of human intestinal epithelium, we demonstrate the regulated expression of EBI3, IL-12p35 and p19 by human intestinal epithelial cells. However, intestinal epithelial cells do not coexpress IL-12p40 or p28 that are required to generate heterodimeric IL-12p75, IL-23 and IL-27. To the extent that IL-12p35, p19 and EBI3 cannot form IL-12p75, IL-23 or IL-27 heterodimers in intestinal epithelial cells, these data suggest that those cells may express other, currently unknown, molecules that can associate with EBI3, IL-12p35 and ⁄or p19 or, alternatively, intestinal epithelial cells may release IL-12-related molecules that by themselves, or in combination with other molecules in the mucosal microenvironment, mediate biological activities.

show abstract

Section: Human Intestinal Xenograftsmentioning

confidence: 99%

Expression of Epstein–Barr virus‐induced gene 3 and other interleukin‐12‐related molecules by human intestinal epithelium

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…44 Conversely, in human intestinal epithelial cell cultures, Cryptosporidium directly activates PGH synthase 2 expression and PGE 2 synthesis by infected cells. 45 The relative contribution of these mechanisms to net PG production in vivo and the signaling pathways leading to altered electrolyte transport need to be resolved, as this may have important therapeutic implications.…”

Section: Role Of Endogenous Prostaglandin (Pg) Synthesismentioning

confidence: 99%

Host Responses to Cryptosporidium Infection

2002

View full text Add to dashboard Cite

Cryptosporidium is a clinically and economically important infection whose pathogenic effect begins with colonization of the intestinal epithelium. Despite intensive efforts, a consistently effective therapy for the infection has yet to be identified. Morbidity and mortality results from ongoing loss of absorptive epithelium, which leads to villous atrophy and malabsorption and release of inflammatory mediators that stimulate electrolyte secretion and diarrhea. With further clarification of the mechanisms underlying enterocyte malfunction in Cryptosporidium infection, it should be possible to design rational nutritional and pharmacologic therapies to enhance nutrient and water absorption, promote the clearance of infected enterocytes, and restore normal villus architecture and mucosal barrier function.

show abstract

“…Due to this "minimally invasive" nature of infection, intestinal epithelium provides the first line of defense and plays a critical role in activating and orchestrating host responses to C. parvum infection (Chen et al 2002). Indeed, the invasion of enterocytes by C. parvum activates the nuclear factor-kappa B (NF-KB) signaling, resulting in the production and secretion of various cytokines and chemokines, antimicrobial peptides (b-defensins and cathelicidins), and nitric oxide, which may kill C. parvum or inhibit parasite growth (Laurent et al 1998;O'Hara and Chen 2011;Zhou et al 2012). In addition, infection increases release of epithelial cellderived exosomes to the lumen and to the basolateral region (Hu et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Cryptosporidium parvum infection attenuates the ex vivo propagation of murine intestinal enteroids

Zhang

Gong

Wang

et al. 2016

Physiological Reports

View full text Add to dashboard Cite

Cryptosporidium, a ubiquitous coccidian protozoan parasite that infects the gastrointestinal epithelium and other mucosal surfaces, is an important opportunistic pathogen for immunocompromised individuals and a common cause of diarrhea in young children in the developing countries. One of the pathological hallmarks of intestinal cryptosporidiosis is villous atrophy, which results in a shorter height of intestinal villi. Here, we investigated the effects of Cryptosporidium infection on intestinal epithelial growth, using an ex vivo model of intestinal cryptosporidiosis employing enteroids from mice. We detected infection of enteroids isolated from immunocompetent adult and neonatal mice after ex vivo exposure to Cryptosporidium sporozoites. We observed a significant inhibition of enteroid propagation following infection. Intriguingly, we identified a decreased expression level of intestinal stem cell markers in enteroids following C. parvum infection. We further measured the expression levels of several Wnt antagonists or agonists in infected enteroids, as induction of the Wnt/β‐catenin activation is a key factor for intestinal stem cell function. We detected a markedly increased level of the Dickkopf‐related protein 1 and decreased level of the Wnt family member 5a in enteroids after infection. The low density lipoprotein receptor‐related protein 5, one of the Wnt co‐receptors, is downregulated in the infected enteroids. In addition, increased apoptotic cell death and cell senescence were observed in the infected enteroids. Our results demonstrate a significant inhibitory effect of Cryptosporidium infection on the ex vivo propagation of enteroids from mice, providing additional insights into the impact of Cryptosporidium infection on intestinal epithelial growth.

show abstract

Human Intestinal Epithelial Cells Respond toCryptosporidium parvumInfection with Increased Prostaglandin H Synthase 2 Expression and Prostaglandin E₂and F_2αProduction

Cited by 85 publications

References 24 publications

Expression of Epstein–Barr virus‐induced gene 3 and other interleukin‐12‐related molecules by human intestinal epithelium

Expression of Epstein–Barr virus‐induced gene 3 and other interleukin‐12‐related molecules by human intestinal epithelium

Host Responses to Cryptosporidium Infection

Cryptosporidium parvum infection attenuates the ex vivo propagation of murine intestinal enteroids

Contact Info

Product

Resources

About