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, LF; INSFRAN, CONSTANZA; VOLPINI, XIMENA; CERVI, LAP; QUINTANA, FRANCISCO; MOTRAN, CLAUDIA C

CABA

Congreso; I meeting LASID SAI FAIC; 2015

LASID SAI

During Chagas disease, parasite persistence and theinappropriately balanced inflammation play important roles inhost tissue damage. Therefore, better understanding about thecellular and molecular mechanisms that promote strong Th1response followed by its timely contraction, is mandatory todesign improved therapeutic strategies. The AhR is a ligandactivatedtranscription factor that plays important roles in severalbiological processes, including development, detoxification andthe immune response. To investigate the role of AhR activated bynatural ligands generated during T.cruzi infection, B6 (WT) miceand B6 mice carrying a mutant AhR protein with reduced affinityfor its ligands (AhRd) were infected with T.cruzi, and parasitemia,survival and splenic T-cell populations were studied at day 10pi.AhRd mice showed significantly lower parasitemia and reducednumber of the Treg cells (consistent with the important role ofAhR signaling on Treg development) associated with anexpansion of CD4+IFN-γ producing cells compared with WTmice. Even though AhRd mice showed an exacerbated Th1-typeresponse (associated to tissue damage) they succumbed later thanWT mice and displayed significantly lower liver damage. Theanalysis of spleen populations at day 17pi showed that the spleensize as well as the Th1-type response remained unchanged inAhRd mice but continued increased in B6 mice. Interestingly, apopulation of CD4+IFN-γ and IL-10 secreting cells, critical tolimit collateral damage in parasitosis, was significantly upregulated in spleen of AhRd mice. Our results show that weakAhR signaling promotes the development of self-regulatory Th1cells during T.cruzi infection.