Deficiency of tumor necrosis factor p55 receptor enhances interferon-gamma and interleukin-17 responses after Yersinia infection.

ETHELINA CARGNELUTTI; RICARDO JAVIER ELIÇABE; MARIA GABRIELA LACOSTE; GABRIEL ADRIAN RABINOVICH; MARIA SILVIA DI GENARO

Viña del Mar Chile

Congreso; 9th Latin American Congress of Immunology; 2009

Asociación Latinoamericana de Inmunología

We previously demonstrated that Yersinia induces reactive arthritis in TNFRp55-/- mice. The aim was elucidate the impact of TNFRp55 deficiency on IFN-g and IL-17 responses. Wild-type C57BL/6 (WT) and TNFRp55-/- mice were orogastrically infected with Yersinia enterocolitica O:3. At different days after infection, IL-17, IFN-g, IL-6 , TGF-b1 and p40 subunit were determined in mesenteric lymph nodes (MLN) and inguinal lymph nodes (ILN) homogenates by ELISA. In addition, adoptive transfer of T cells was performed from Yersinia-infected TNFRp55-/- to naive WT, TNFRp55-/- or p40-/- mice; then, these mice were challenged with heat-killed Yersinia (HKY) and delayed-type hypersensitivity (DTH) was determined. We found higher IL-17 and IFN-g levels in TNFRp55-/- compared with WT mice in MLN (p < 0.001 and p < 0.01, respectively); and in ILN (p < 0.01). IL-17 levels correlated with increased IL-6 and TGF-b1 concentrations (p < 0.05). Accordingly, augmented p40 level was detected in TNFRp55-/- mice (p < 0.05). Higher DTH response was observed in TNFRp55-/- mice after adoptive transfer (p < 0.05). We concluded that in the absence of TNFRp55 signaling, Th1 and Th17 responses may act in concert to sustain the inflammatory response, and p40 may be involved in the generation of these effector cells.