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THE IMPACT OF THE CTHRSSVVC PEPTIDE UPON EXPERIMENTAL MODELS OF TRYPANOSOMA CRUZI INFECTION
Doença de Chagas
Quimioterapia experimental
Imunomodulação
Peptídeo CTHRSSVVC
Trypanosoma cruzi
Experimental chemotherapy
CTHRSSVVC peptide
Immunomodulation
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular,. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular,. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular,. Rio de Janeiro, RJ, Brasil / Universidade do Estado de Minas Gerais. Laboratório de Parasitologia Aplicada. Unidade Passos, Belo Horizonte, MG, Brasil.
Universidade de São Paulo (HCFMUSP. Faculdade de Medicina. Hospital das Clínicas. São Paulo, SP, Brasil.
Instituto de Pesquisas Nucleares e Energéicas (IPEN), CNEN. São Paulo, SP. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular,. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular,. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular,. Rio de Janeiro, RJ, Brasil / Universidade do Estado de Minas Gerais. Laboratório de Parasitologia Aplicada. Unidade Passos, Belo Horizonte, MG, Brasil.
Universidade de São Paulo (HCFMUSP. Faculdade de Medicina. Hospital das Clínicas. São Paulo, SP, Brasil.
Instituto de Pesquisas Nucleares e Energéicas (IPEN), CNEN. São Paulo, SP. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular,. Rio de Janeiro, RJ, Brasil.
Abstract
Chagas disease (CD), caused by the hemoflagellate protozoan Trypanosoma cruzi, affects
more than six million people worldwide and presents an unsatisfactory therapy, based on
two nitroderivatives, introduced in clinical medicine for decades. The synthetic peptide,
with CTHRSSVVC sequence (PepA), mimics the CD163 and TNF-a tripeptide “RSS” motif
and binds to atheromatous plaques in carotid biopsies of human patients, spleen tissues,
and a low-density lipoprotein receptor knockout (LDLr−/−) mouse model of
atherosclerosis. CD163 receptor is present on monocytes, macrophages, and
neutrophils, acting as a regulator of acute-phase processes and modulating aspects of
the inflammatory response and the establishment of infections. Due to the potential
theranostic role of PepA, our aim was to investigate its effect upon T. cruzi infection in vitro
and in vivo. PepA and two other peptides with shuffled sequences were assayed upon
different binomials of host cell/parasite, including professional [as peritoneal mouse
macrophages (PMM)] and non-professional phagocytes [primary cultures of cardiac
cells (CM)], under different protocols. Also, their impact was further addressed in vivo
using a mouse model of acute experimental Chagas disease. Our in-vitro findings
demonstrate that PepA and PepB (the peptide with random sequence retaining the
“RS” sequence) reduced the intracellular parasitism of the PMM but were inactive during
the infection of cardiac cells. Another set of in-vitro and in-vivo studies showed that they
do not display a trypanocidal effect on bloodstream trypomastigotes nor exhibit in-vivo
efficacy when administered after the parasite inoculation. Our data report the in-vitro
activity of PepA and PepB upon the infection of PMM by T. cruzi, possibly triggering the
microbicidal arsenal of the host professional phagocytes, capable of controlling parasitic
invasion and proliferation.
Keywords in Portuguese
Trypanosoma cruziDoença de Chagas
Quimioterapia experimental
Imunomodulação
Peptídeo CTHRSSVVC
Keywords
Chagas diseaseTrypanosoma cruzi
Experimental chemotherapy
CTHRSSVVC peptide
Immunomodulation
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