Congenic AhRd mice orchestrate an appropriate timing between inflammatory and anti-inflammatory factors that can restrict T. cruzi spreading without extensive collateral damage to the host.

AMBROSIO LAURA FERNANDA; CONSTANZA INSFRÁN; VOLPINI XIMENA; CERVI LAURA; QUINTANA FRANCISCO; MOTRAN CLAUDIA CRISTINA

Buenos Aires

Congreso; LXIII Reunion Anual de la Sociedad Argentina de Inmunología; 2015

Sociedad Argentina de Inmunología

During Chagasdisease, parasite persistence and theinappropriately balanced inflammation play important roles in host tissuedamage. Therefore, betterunderstanding about the cellular and molecular mechanisms that promote strongTh1 response followed by its timely contraction, is mandatory to designimproved therapeutic strategies.  TheAhR is a ligand-activated transcription factor that plays important roles inseveral biological processes, including development, detoxification and theimmune response.  To investigate the roleof AhR activated by natural ligands generated during T.cruzi infection, B6 (WT) mice and B6 mice carrying a mutant AhRprotein with reduced affinity for its ligands (AhRd) were infected with T.cruzi, and parasitemia, survival andsplenic T-cell populations were studied at day 10pi. AhRd mice showedsignificantly lower parasitemia and reduced number of the Treg cells(consistent with the important role of AhR signaling on Treg development) associatedwith an expansion of CD4+ IFN-γ producing cells compared with WT mice.  Even though AhRd mice showed an exacerbatedTh1-type response (associated to tissue damage) they succumbed later than WTmice and displayed significantly lower liver damage.  The analysis of spleen populations at day 17pi showed that the spleen size as well as the Th1-type response remainedunchanged in AhRd mice but continued increased in B6 mice.  Interestingly, a population of CD4+ IFN-γ and IL-10 secreting cells, critical to limit collateral damage in parasitosis, wassignificantly up regulated in spleen of AhRd mice.  Our results show that weak AhR signalingpromotes the development of self-regulatory Th1 cells during T.cruzi infection.