Role of indoleamine 2,3-dioxygenase (IDO) in testicular immune-privilege

GISELA S. GUALDONI; PATRICIA V. JACOBO; CRISTIAN M. SOBARZO; CHRISTIAN HOCHT; MARCELO HILL; IGNACIO ANEGON; LIVIA LUSTIG; VANESA A. GUAZZONE

Medellin

Congreso; ALAI, XI Congress. INMUNOCOLOMBIA 2015; 2015

ProblemThe production, differentiation, and presence of male gametes represent inimitable challenge to immune system, as they appear long after the establishment of normal immune tolerance mechanisms. The ability of the testes to tolerate autoantigenic germ cells as well as survival in the testicular interstitium of transplanted foreign tissues has led to the testis being considered an immunologically privileged site. Disruption of the immune privilege status following trauma, tumor, or autoimmune orchitis often results in male infertility. There is strong evidence that IDO mediates potent immunosupression in classical immune responses as well as in fetal tolerance, tumor immune resistance, and regulation of autoimmunity. However, in spite of considerable progress the relevance of IDO in testis pathophysiology have not yet been explored. Here we evaluated the in vivo role of IDO in experimental autoimmune orchitis (EAO), a well-established model of autoimmune testicular inflammation associated with subfertility and infertility Method of StudyEAO was induced in adult Wistar rats with testicular homogenate and adjuvants. Control (C) rats injected with saline and adjuvants, and normal untreated rats (N) were also studied. IDO localization and level of expression in the testis was analyzed by immunostaining and Western blot, respectively. Testis tryptophan and kynurenine concentrations were measured by HPLC. To inhibit IDO, EAO rats received 1-methyl-tryptophan during the immunization period.ResultsA similar localization of IDO expression was detected in N, C and EAO rats. In testicular interstitium, IDO was detected in mononuclear and endothelial cells. A reduced IDO expression was detected, by Western blot, in seminiferous tubule fractions from EAO compared with N and C rats. This phenomenom was concomitant to a significant reduction of tryptophan-degrading activity in EAO testis. In vivo inhibition of IDO increased the severity of the disease.ConclusionOur results unveil a down regulation of IDO-based tolerance when testicular immune privilege is disrupted.