THE AUTOIMMUNE RESPONSE ELICITED BY MOUSE HEPATITIS VIRUS (MHV-A59) INFECTION IS MODULATED BY LIVER TRYPTOPHAN-2,3- DIOXYGENASE (TDO)

MOHAMED F. MANDOUR; JOSÉ L. APARICIO; M DUHALDE VEGA; LILIA A. RETEGUI

IMMUNOLOGY LETTERS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2019

0165-2478

In a previous work we demonstrated that inhibition of mouse indoleamine 2,3-dioxygenase (IDO)by methyltryptophan (MT) exacerbated the pathological actions of mouse hepatitis virus (MHVA59)infection, suggesting that tryptophan (TRP) catabolism was involved in viral effects. Sincethere is a second enzyme that dioxygenates TRP, tryptophan-2, 3-dioxygenase (TDO), which ismainly located in liver, we decided to study its role in our model of MHV-infection.Results showed that in vivo TDO inhibition by LM10, a derivative of 3-(2-(pyridyl) ethenyl) indole,resulted in a decrease of anti- MHV Ab titers induced by the virus infection. Besides, a reductionof some alarmin release, i.e, uric acid and high-mobility group box1 protein (HMGB1), wasobserved. Accordingly, since alarmin liberation was related to the expression of autoantibodies(autoAb) to fumarylacetoacetate hydrolase (FAH), these autoAb also diminished. Moreover, PCRresults indicated that TDO inhibition did not abolish viral replication. Furthermore, histologicalliver examination did not reveal strong pathologies, whereas mouse survival was hundred percent incontrol as well as in MHV-infected mice treated with LM10.Data presented in this work indicate that in spite of the various TDO actions already described,specific TDO blockage could also restrain some MHV actions, mainly suppressing autoimmunereactions. Such results should prompt further experiments with various viruses to confirm thepossible use of a TDO inhibitor such as LM-10 to treat either viral infections or even autoimmunediseases triggered by a viral infection.