Cryptosporidium parvum increases intestinal permeability through interaction with epithelial cells and IL-1β and TNFα released by inflammatory monocytes.
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.
ISP, INRA, Université Tours, 37380, Nouzilly, France.
Thibaut
T
de Sablet
ISP, INRA, Université Tours, 37380, Nouzilly, France.
Laurent
L
Potiron
ISP, INRA, Université Tours, 37380, Nouzilly, France.
Mathilde
M
Marquis
ISP, INRA, Université Tours, 37380, Nouzilly, France.
Françoise I
FI
Bussière
ISP, INRA, Université Tours, 37380, Nouzilly, France.
Sonia
S
Lacroix-Lamandé
ISP, INRA, Université Tours, 37380, Nouzilly, France.
Fabrice
F
Laurent
D000818:Animals; D000831:Animals, Newborn; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D015820:Cadherins / Q000235:genetics / Q000276:immunology; D003457:Cryptosporidiosis / Q000235:genetics / Q000276:immunology / Q000469:parasitology*; D016785:Cryptosporidium parvum / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000276:immunology / Q000469:parasitology*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000469:parasitology; D010539:Permeability; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D051176:beta Catenin / Q000235:genetics / Q000276:immunology
D000950:Antigens, Ly; C495267:CTNNB1 protein, mouse; D015820:Cadherins; C000611838:Cdh1 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; C494192:Ly-6C antigen, mouse; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin