Cryptosporidium parvumincreases intestinal permeability through interaction with epithelial cells and IL-1β and TNFα released by inflammatory monocytes

Abstract

Intestinal epithelial cells form a single layer separating the intestinal lumen containing nutriments and microbiota from the underlying sterile tissue and therefore play a key role in maintaining homeostasis. We investigated the factors contributing to the alteration of the epithelial barrier function during Cryptosporidium parvum infection. Infected polarized epithelial cell monolayers exhibit a drop in transepithelial resistance associated with a delocalization of E-cadherin and β-catenin from their intercellular area of contact, the adherens junction complex. In neonatal mice infected by C. parvum, the increased permeability is correlated with parasite development and with an important recruitment of Ly6c inflammatory monocytes to the subepithelial space. TNFα and IL-1β produced by inflammatory monocytes play a key role in the loss of barrier function. Our findings demonstrate for the first time that both the parasite and inflammatory monocytes contribute to the loss of intestinal barrier function during cryptosporidiosis.

Interplay between gut microbiota and p66Shc affects obesity‐associated insulin resistance

“…In p66Shc 2/2 mice, expression of Il-1b and of the antimicrobial peptideencoding gene Reg3g was increased on SD and was demodulated after HFD. IL-1b is a major determinant of intestinal inflammation and permeability (23), and lectins encoded by the Reg3g gene determine bacterial adherence to the mucosa, translocation, and gut inflammation (24). Although we found no overt sign of colitis or a significant increase in permeability, we cannot exclude the notion that proinflammatory gene expression accompanies dysbiosis in the gut of p66Shc 2/2 vs. WT mice.…”

Association of enteric parasitic infections with intestinal inflammation and permeability in asymptomatic infants of São Tomé Island

“…Parasitic enteric pathogens can disrupt the intestinal barrier directly, by binding to cell surface molecules, causing cell damage and apoptosis, or by disrupting tight junctions and cell cytoskeleton [9,10] as described in Cryptosporidium spp. [11,12], G. duodenalis [13,14] and STH infections [15,16]. The severity of the intestinal inflammatory response is variable and dependent on the immune status of the host, parasite invasive potential, and ecological niche [17].…”

“…In this cohort study, follow-up was scheduled for anthropometric measurements, neurodevelopment assessment, and intestinal parasites examination, approximately at 3,6,9,12,16,18, and 24 months of age. To assess the cumulative exposure to enteric parasitic infections, a minimum of four points of assessment (at 6, 12, 18 and 24 months) were required, which coincided with semestral appointments for feeding advice and scheduled immunizations.…”

Lessons Learned from Protective Immune Responses to Optimize Vaccines against Cryptosporidiosis

“…Chemokines are first released by C. parvum -infected IECs to promote chemotaxis at the site of infection; chemokines induce migration of dendritic cells in the ileum and the draining lymph nodes [ 40 ] ( Figure 1 ). Inflammatory monocytes will also migrate to the subepithelial space in response to C. parvum infection and secrete TNFα and IL-1β [ 41 ]. These cytokines will increase permeability, therefore weakening the integrity of the intestinal epithelial barrier [ 41 ].…”

“…Inflammatory monocytes will also migrate to the subepithelial space in response to C. parvum infection and secrete TNFα and IL-1β [ 41 ]. These cytokines will increase permeability, therefore weakening the integrity of the intestinal epithelial barrier [ 41 ]. Also, nitric oxide NO is important in C. parvum infection clearance and reduces oocyst shedding in chronically infected nude mice [ 42 ].…”