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IN THE ACUTE PHASE OF TRYPANOSOMA CRUZI INFECTION, LIVER LYMPHOID AND MYELOID CELLS DISPLAY AN AMBIGUOUS PHENOTYPE COMBINING PRO- AND ANTI-INFLAMMATORY MARKERS
Infecção por Trypanosoma cruzi
Tolerância imunológica
Fígado
Inflamação
Trypanosoma cruzi infection
Immunological tolerance
Liver
Inflammation
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, United States.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, United States.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Abstract
Multiple cell populations, cellular biochemical pathways, and the autonomic nervous
system contribute to maintaining the immunological tolerance in the liver. This tolerance is
coherent because the organ is exposed to high levels of bacterial pathogen-associated
molecular pattern (PAMP) molecules from the intestinal microbiota, such as
lipopolysaccharide endotoxin (LPS). In the case of Trypanosoma cruzi infection,
although there is a dramatic acute immune response in the liver, we observed
intrahepatic cell populations combining pro- and anti-inflammatory markers. There was
loss of fully mature Kupffer cells and an increase in other myeloid cells, which are likely to
include monocytes. Among dendritic cells (DCs), the cDC1 population expanded relative
to the others, and these cells lost both some macrophage markers (F4/80) and
immunosuppressive cytokines (IL-10, TGF-b1). In parallel, a massive T cell response
occured with loss of naïve cells and increase in several post-activation subsets. However,
these activated T cells expressed both markers programmed cell death protein (PD-1) and
cytokines consistent with immunosuppressive function (IL-10, TGF-b1). NK and NK-T
cells broadly followed the pattern of T cell activation, while TCR-gd cells appeared to be
bystanders. While no data were obtained concerning IL-2, several cell populations also
synthesized IFN-g and TNF-a, which has been linked to host defense but also to tissue
injury. It therefore appears that T. cruzi exerts control over liver immunity, causing T cell
activation via cDC1 but subverting multiple populations of T cells into immunosuppressive
pathways. In this way, T. cruzi engages a mechanism of hepatic T cell tolerance that is
familiar from liver allograft tolerance, in which activation and proliferation are followed by
T cell inactivation.
Keywords in Portuguese
Resposta imune hepáticaInfecção por Trypanosoma cruzi
Tolerância imunológica
Fígado
Inflamação
Keywords
Hepatic immune responseTrypanosoma cruzi infection
Immunological tolerance
Liver
Inflammation
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