Role of TNFRp55 in Yersinia enterocolitica O:3-induced arthritis: triggering bacterial antigens and articular immune response

Genaro, María Silvia Di; Cargnelutti, Diego Esteban; Eliçabe, J R; Lacoste, María Gabriela; Valdéz, Susana R.; Gómez, Nora; Guzmán, A.M.

doi:10.1093/rheumatology/kel348

Cited by 10 publications

(21 citation statements)

References 21 publications

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“…However, TNF is also a critical cytokine in the protective host response against bacterial infection, including Y. enterocolitica (5,24), raising the question as to whether this cytokine plays a pathogenic or protective role in bacterial-induced ReA, a pathological entity that combines components of infection and autoimmunity. We recently demonstrated that TNFR p55 signaling confers protection against ReA induced by Y. enterocolitica O:3 (8). In addition, unfavorable evolution has been reported in patients with spondyloarthropathies under treatment with TNF blockers (37).…”

Section: Discussionmentioning

confidence: 99%

“…Bacteria were cultured as described earlier (8). Mice were starved for 8 h and then were infected orogastrically, with 1-5 3 10 8 yersiniae in 200 ml saline, using a gastric tube.…”

Section: Bacterial Culture and Infectionmentioning

confidence: 99%

“…Mouse IL-17, IFN-g, IL-6, IL-1b, TGF-b 1 , IL-12/IL-23 p40, IL-12p70, IL-23 (p19/p40), and IL-10 were determined in the joint, mesenteric lymph node (MLN), and inguinal lymph node (ILN) homogenates, prepared as described previously (8), as well as in spleen cell culture supernatants using capture ELISA kits (eBioscience, San Diego, CA), according to the manufacturer's instructions. The limit of detection for the above-mentioned cytokines was 4 pg/ml for IL-17, 0.7 pg/ml for IFN-g, 4 pg/ml for IL-6, 8 pg/ml for IL-1b, 60 pg/ml for TGF-b 1 , 2 pg/ml for IL-12/IL-23 p40, 30 pg/ml for IL-23 (p19/p40), and 30 pg/ml for IL-10.…”

Section: Cytokine Determination By Elisamentioning

confidence: 99%

“…Moreover, in recent studies, we found that TNFR p55 signaling also plays a protective role against ReA induced by Y. enterocolitica O:3 (8). To further dissect the mechanisms involved in this protective effect, we first examined disease progression in…”

Section: Impact Of Tnfr P55 Deficiency On the Development Of Chronic mentioning

confidence: 99%

“…Given the dual role of TNF as a pathogenic or hostprotective factor in autoimmune or microbial settings, the pathological relevance of this cytokine in ReA remains unclear. In this regard, we previously found that TNFR p55-driven immuneprotective mechanisms prevent the evolution to ReA upon oral infection with Y. enterocolitica O:3, the most frequently associated human arthritogenic serotype (8). Interestingly, TNFR p55-deficient (TNFRp55 2/2 ) mice develop severe chronic arthritis compared with their wild-type (WT) counterparts (8); however, the mechanisms underlying these pathogenic effects remain uncertain.…”

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confidence: 99%

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Lack of TNFR p55 Results in Heightened Expression of IFN-γ and IL-17 during the Development of Reactive Arthritis

Eliçabe¹,

Cargnelutti²,

Serer³

et al. 2010

The Journal of Immunology

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Reactive arthritis (ReA) is a type of arthritis originating from certain gastrointestinal or genitourinary infections. In previous studies, we reported the development of progressive Yersinia enterocolitica-induced ReA in mice lacking TNFR p55; however, the mechanisms underlying this effect are still uncertain. In this study, we investigated the impact of TNFR p55 deficiency in modulating Ag-specific Th1 and Th17 responses during this arthritogenic process. We found more severe ReA in TNFRp55−/− mice compared with their wild-type (WT) counterparts. This effect was accompanied by increased levels of Yersinia LPS in the joints of knockout mice. Analysis of the local cytokine profile revealed greater amounts of IFN-γ and IL-17 in arthritic joints of TNFRp55−/− mice compared with WT mice at day 21 postinfection. Moreover, altered IL-17 and IFN-γ production was observed in mesenteric and inguinal lymph nodes of Yersinia-infected TNFRp55−/− mice, as well as in spleen cells obtained from infected mice and restimulated ex vivo with bacterial Ags. Increased levels of cytokine secretion were associated with a greater frequency of CD4+IL-17+, CD4+IFN-γ+, and IL-17+IFN-γ+ cells in TNFRp55−/− mice compared with WT mice. Remarkably, Ab-mediated blockade of IL-17 and/or IFN-γ resulted in reduced joint histological scores in TNFRp55−/− mice. A mechanistic analysis revealed the involvement of p40, a common subunit of heterodimeric IL-12 and IL-23, in the generation of augmented IFN-γ and IL-17 production under TNFR p55 deficiency. Taken together, these data indicate that, in the absence of TNFR p55 signaling, Th1 and Th17 effector cells may act in concert to sustain the inflammatory response in bacterial-induced arthritogenic processes.

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Section: Discussionmentioning

confidence: 99%

“…Bacteria were cultured as described earlier (8). Mice were starved for 8 h and then were infected orogastrically, with 1-5 3 10 8 yersiniae in 200 ml saline, using a gastric tube.…”

Section: Bacterial Culture and Infectionmentioning

confidence: 99%

Section: Cytokine Determination By Elisamentioning

confidence: 99%

Section: Impact Of Tnfr P55 Deficiency On the Development Of Chronic mentioning

confidence: 99%

mentioning

confidence: 99%

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