title: Salmonella enterica induces joint inflammation and expression of interleukin-17 in draining lymph nodes early after onset of enterocolitis in mice.
abstract: In developing countries, one-third of reactive arthritis (ReA) cases are associated with Salmonella enterocolitis; nevertheless, there is no animal model for studying this pathology. Here we induced a self-limiting Salmonella enterica serovar Enteritidis enterocolitis in mice to analyze the onset of ReA. BALB/c mice received orally 20 μg of streptomycin 24 h before intragastric inoculation of a low dose (3 × 10(3) to 4 × 10(3) CFU) of S. Enteritidis. In response to Salmonella infection, a 30-fold increase in the expression of interleukin-17 (IL-17), measured by quantitative PCR, was observed in mesenteric lymph nodes 5 days postinfection. At this time synovitis was already evident, and concomitantly, a significant increase in joint tumor necrosis factor alpha (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). The early development of joint lesions was accompanied by an increased expression of IL-17 in inguinal and popliteal lymph nodes. Infection with 10(7) CFU of an isogenic ΔinvG mutant bearing a defective type III secretion system of Salmonella encoded in the pathogenicity island 1 apparatus (TTSS-1) induced enterocolitis histologically similar to that triggered by the wild-type strain. Interestingly, despite the higher infective dose used, the mutant did not trigger intestinal IL-17. Moreover, no synovitis was observed in mice suffering ΔinvG enterocolitis. Neutralization of IL-17 in mice infected with S. Enteritidis prevented both synovitis and the increment of TNF-α in the joints, suggesting that IL-17 participates in the generation of Salmonella-induced ReA through the induction of TNF-α in the joints.
authors.affiliation: Instituto de Microbiología y Parasitología Médica (IMPAM-CONICET) and Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Mariángeles
authors.initials: M
authors.lastname: Noto Llana
authors.forename: Sebastián Hernán
authors.initials: SH
authors.lastname: Sarnacki
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Vázquez
authors.forename: Alejandra Sonia
authors.initials: AS
authors.lastname: Gartner
authors.forename: Mónica Nancy
authors.initials: MN
authors.lastname: Giacomodonato
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Cerquetti
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000209:etiology* / Q000276:immunology; D004760:Enterocolitis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000473:pathology; D019779:Salmonella enterica / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha