Recombinant Salmonella typhimurium outer membrane protein A is recognized by synovial fluid CD8 cells and stimulates synovial fluid mononuclear cells to produce interleukin (IL)‐17/IL‐23 in patients with reactive arthritis and undifferentiated spondyloarthropathy. (23rd May 2016)

• Record Type: Journal Article
• Authors: Chaurasia, S.; Shasany, A. K.; Aggarwal, A.; Misra, R.
• Is Part Of: Clinical and experimental immunology. Volume 185:Number 2(2016:Aug.)
• Page Start: 210
• Page End: 218
• Publication Date: 2016-05-23
• Subjects: antigens -- arthritis -- bacterial -- cytotoxic T cells -- cytokines; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12799
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: In developing countries, one‐third of patients with reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) are triggered by Salmonella typhimurium . Synovial fluid mononuclear cells (SFMCs) of patients with ReA and uSpA proliferate to low molecular weight fractions (lmwf) of outer membrane proteins (Omp) of S. typhimurium . To characterize further the immunity of Omp of Salmonella, cellular immune response to two recombinant proteins of lmwf, OmpA and OmpD of S. typhimurium (rOmpA/D‐sal) was assessed in 30 patients with ReA/uSpA. Using flow cytometry, 17 of 30 patients' SF CD8 + T cells showed significant intracellular interferon (IFN)‐γ to Omp crude lysate of S. typhimurium . Of these 17, 11 showed significantly more CD8 + CD69 + IFN‐γ T cells to rOmpA‐sal, whereas only four showed reactivity to rOmpD‐sal. The mean stimulation index was significantly greater in rOmpA‐sal than rOmpD‐sal [3·0 (1·5–6·5) versus 1·5 (1·0–2·75), P < 0·005]. Similarly, using enzyme‐linked immunospot (ELISPOT) in these 17 patients, the mean spots of IFN‐γ‐producing SFMCs were significantly greater in rOmpA‐sal than rOmpD‐sal [44·9 (3·5–130·7) versus 19·25 (6–41), P < 0·05]. SFMCs stimulated by rOmpA‐sal produced significantly more proinflammatory cytokines than rOmpD‐sal: IFN‐γ [1·44 (0·39–20·42) versus 0·72 (0·048–9·15) ng/ml, P < 0·05], interleukin (IL)−17 [28·60 (6·15–510·86) versus 11·84 (6·83–252·62) pg/ml, P < 0·05], IL‐23 [70·19 (15–1161·16) versus 28·25 (> 15–241·52) pg/ml, P < 0·05] and IL‐6 [59·78 (2·03–273·36) versus 10·17 (0·004–190·19) ng/ml, P < 0·05]. The rOmpA‐sal‐specific CD8 + T cell response correlated with duration of current synovitis ( r = 0·53, P < 0·05). Thus, OmpA of S. typhimurium is a target of SF CD8 + T cells and drives SFMC to produce increased cytokines of the IL‐17/IL‐23 axis which contribute to the pathogenesis of Salmonella‐ triggered ReA.