EFFECTS OF INTERLEUKIN 17A (IL-17A) NEUTRALIZATION ON MURINE HEPATITIS VIRUS (MHV-A59) INFECTION

APARICIO, JL; OTTOBRE M; DUHALDE VEGA, MAITE; UYTTENHOVE C; COUTELIER JP; RETEGUI LA

EUROPEAN CYTOKINE NETWORK

JOHN LIBBEY EUROTEXT LTD

Año: 2017

1148-5493

Mice infected with mouse hepatitis virus A59 (MHV-A59) develop hepatitis, thymus involution, IgG2a-restricted hypergammaglobulinaemia and a concomitant enhancement of plasmatic transaminase levels. Viral infection also induces autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH), a fact closely related to the release of alarmins such as uric acid and/or high-mobility group box protein 1 (HMGB1). It was reported that Interleukin 17 (IL-17) exerts a host-defensive role in many infectious diseases and is involved in inflammatory pathologies and autoimmunity. Thus, we studied the effect of neutralizing monoclonal antibodies (MAb) against IL-17, in our model of mouse MHV-infection. MAb anti IL-17F and anti-IFNγ were used as complements of the study.Results showed that transaminase levels dramatically decreased in MHV-infected mice treated with MAb anti-IL-17A whereas plasmatic Ig concentration sharply increased. Conversely, MAb anti-IL-17F enhanced transaminase liberation and did not affect Ig levels.Serum IFNγ was detected in mice submitted to MHV-infection, and the cytokine concentration did increase significantly after MAb anti IL-17A administration. Besides, MAb anti-IFNγ greatly augmented transaminase plasmatic levels. However, the simultaneous administration on both MAb produced a sharply diminution of transaminase release. Furthermore, treatment with MAb anti-IL-17A and/or MAb anti-IFNγ augmented plasmatic Ig concentration in MHV-infected mice. IL-17A neutralization did not affect MHV-induction of HMGB1 liberation and slightly augmented plasmatic uric acid concentration. However, mice treated with the MAb failed to produce autoAb to FAH. Thus, results suggest that, although uric acid or HMGB1 liberation are necessary for the induction of autoAb to FAH, the adjuvant action of both alarmins could be expressed thanks to the presence of IL-17A. Besides, treatment with MAb anti-IL-17F or IFNγ also abolish autoAb to FAH.The above results suggest a reciprocal regulation of Th1 and Th17 cells, acting on the different MHV effects such as release of liver transaminases and hypergamaglobulinema, and a certain orchestration between IL-17A and uric acid and /or HMGB1to allow expression of autoAb.