title: Vibrio cholerae-induced inflammation in the neonatal mouse cholera model.
abstract: Vibrio cholerae is the causative agent of the acute diarrheal disease of cholera. Innate immune responses to V. cholerae are not a major cause of cholera pathology, which is characterized by severe, watery diarrhea induced by the action of cholera toxin. Innate responses may, however, contribute to resolution of infection and must be required to initiate adaptive responses after natural infection and oral vaccination. Here we investigated whether a well-established infant mouse model of cholera can be used to observe an innate immune response. We also used a vaccination model in which immunized dams protect their pups from infection through breast milk antibodies to investigate innate immune responses after V. cholerae infection for pups suckled by an immune dam. At the peak of infection, we observed neutrophil recruitment accompanied by induction of KC, macrophage inflammatory protein 2 (MIP-2), NOS-2, interleukin-6 (IL-6), and IL-17a. Pups suckled by an immunized dam did not mount this response. Accessory toxins RtxA and HlyA played no discernible role in neutrophil recruitment in a wild-type background. The innate response to V. cholerae deleted for cholera toxin-encoding phage (CTX) and part of rtxA was significantly reduced, suggesting a role for CTX-carried genes or for RtxA in the absence of cholera toxin (CTX). Two extracellular V. cholerae DNases were not required for neutrophil recruitment, but DNase-deficient V. cholerae caused more clouds of DNA in the intestinal lumen, which appeared to be neutrophil extracellular traps (NETs), suggesting that V. cholerae DNases combat NETs. Thus, the infant mouse model has hitherto unrecognized utility for interrogating innate responses to V. cholerae infection.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine and Howard Hughes Medical Institute, Boston, Massachusetts, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Bishop
authors.forename: Bharathi
authors.initials: B
authors.lastname: Patimalla
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
mesh_terms: D000818:Animals; D015415:Biomarkers; D002771:Cholera / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000276:immunology*; D007114:Immunization; D007249:Inflammation / Q000276:immunology*; D007421:Intestine, Small; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D014734:Vibrio cholerae / Q000276:immunology*
chemical_list: D015415:Biomarkers; D016207:Cytokines