T. cruzi infection interferes with thymic regulatory T cell homeostasis

GONZALEZ F; CALMON HAMATY F; SEARA CORDEIRO SN; FERNANDEZ BUSSY R; SPINELLI S; D´ATTILIO L; BOTTASSO O; SAVINO W; COTTA DE ALMEIDA V; VILLAR S; PEREZ A

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2016 vol. 10 p. 1 - 10

1935-2735

The dynamics of regulatory T cells throughout the course of Trypanosoma cruzi infection is still debated. We previously demonstrated that acute murine T. cruzi infection results in an impaired peripheral CD4+Foxp3+ T cell differentiation due to the acquisition of an abnormal Th1-like phenotype and altered functional features, which negatively impact on the course of infection. Moreover, T. cruzi infection induces an intense thymic atrophy. As known, the thymus is the primary lymphoid organ in which thymic-derived regulatory T cells, known as tTregs, differentiate. Considering the lack of available data about the effect of T. cruzi infection upon tTregs, we examined here the tTreg dynamics during the course of disease. We confirmed that T. cruzi infection induces a marked loss of tTregs cell number associated to cell precursor exhaustion and survival factor depletion. At the same time, tTregs accumulate inside the CD4 single-positive compartment exhibiting an increased Ki-67/Annexin V ratio. After infection, tTregs had an enhanced expression of signature markers -CD25, CD62L and GITR- in addition to displaying alterations in the expression of migration-associated molecules (alpha chains of VLAs and chemokine receptors) such as fibronectin-driven migratory abnormalities. Taken together, we provided the first data demonstrating profound alterations in tTreg compartment during acute murine T. cruzi infection, denoting that their homeostasis is profoundly affected. The evident loss of tTregs number may compromise the composition of the peripheral pool of tTregs. If sustained over time such alterations may be related to the immune dysregulations seen in the chronic phase of this disease.