immunology of infectious and parasitic diseases - XXXVII Congress ...

CASPASE-1 AND NLRP3 CONTRIBUTE TO THE CONTROL OF T. cruzi
VIRGINIA MENDES GONÇALVES (PG) 1 ; KELY CATARINE MATTEUCCI (IC) 1
KARINA RAMALHO BORTOLUCI (PI) 1
1 Departamento de Ciências Biológicas e Centro de Terapia Celular e Molecular
(CTC-Mol), Universidade Federal de São Paulo, São Paulo, Brasil.
Introduction: Trypanosoma cruzi is an intracellular protozoan parasite and
etiological agent of Chagas disease, a severe and chronic infectious illness that
affects millions of people in the world. Although the role of TLR in controlling
infection by T. cruzi is well described in the literature, there is no data about the
involvement of inflammasomes.
Methods and Results: In this study, we evaluated the participation of NLRP3
and caspase-1 in host response to T. cruzi infection and found that NLRP3 -/-
and caspase1 -/- mice are susceptible to infection. To determine the mechanisms
involved in susceptibility by NLRP3 -/- and caspase-1 -/- mice, we evaluated
cytokine and nitric oxide (NO) production by spleen cells from infected mice.
Inflammatory cytokines IL-6 and IFN- were found in spleen cells from NLRP3 -/-
and caspase1 -/- infected mice, but these mice displayed a defect in the
production of NO and IL-1. Finally, the inhibition of caspase-1 with z-YVADfmk,
but not the neutralization of IL-1R abrogated the NO production by WT
cells. .
Conclusion: Together, these data show that NLRP3 and caspase-1 are
involved in the control of T. cruzi infection through the induction of NO
production. Moreover, NO production induced by NLRP3 requires active
caspase-1 but it is independent of IL-1R.
Financial support: CAPES, CNPq, FAPESP.