title: Poly(I:C)-induced protection of neonatal mice against intestinal Cryptosporidium parvum infection requires an additional TLR5 signal provided by the gut flora.
abstract: The neonatal intestinal immune system is still undergoing development at birth, leading to a higher susceptibility to mucosal infections. In this study, we investigated the effect of poly(I:C) on controlling enteric infection by the protozoan Cryptosporidium parvum in neonatal mice. After poly(I:C) administration, a rapid reduction in parasite burden was observed and proved to be dependent on CD11c(+) cells and TLR3/TRIF signaling. Protection against C. parvum required additional signals provided by the gut flora through TLR5 and MyD88 signaling. This cooperation gave rise to higher levels of expression of critical mutually dependent cytokines such as interleukin 12p40 and type 1 and type 2 interferons, the last 2 being known to play a key role in the elimination of infected enterocytes. Our findings demonstrate in neonatal mice how gut flora synergizes with poly(I:C) to elicit protective intestinal immunity against an intracellular pathogen.
authors.affiliation: INRA Val de Loire, UMR1282 Infectiologie et Santé Publique, Nouzilly.
authors.forename: Louis
authors.initials: L
authors.lastname: Lantier
authors.forename: Françoise
authors.initials: F
authors.lastname: Drouet
authors.forename: William
authors.initials: W
authors.lastname: Guesdon
authors.forename: Roselyne
authors.initials: R
authors.lastname: Mancassola
authors.forename: Coralie
authors.initials: C
authors.lastname: Metton
authors.forename: Richard
authors.initials: R
authors.lastname: Lo-Man
authors.forename: Catherine
authors.initials: C
authors.lastname: Werts
authors.forename: Fabrice
authors.initials: F
authors.lastname: Laurent
authors.forename: Sonia
authors.initials: S
authors.lastname: Lacroix-Lamandé
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D003457:Cryptosporidiosis / Q000517:prevention & control*; D016785:Cryptosporidium parvum / Q000276:immunology*; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D011070:Poly I-C / Q000008:administration & dosage*; D015398:Signal Transduction; D051198:Toll-Like Receptor 5 / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051198:Toll-Like Receptor 5; D011070:Poly I-C
keywords: Cryptosporidium parvum; TLR3; dendritic cells; intestine; microbiota; neonatal mice; poly(I:C)