Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms

Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion. Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acute parasite infections is uncertain. In this s...

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Detalles Bibliográficos
Autores principales: Poncini, C.V., Ilarregui, J.M., Batalla, E.I., Engels, S., Cerliani, J.P., Cucher, M.A., Van Kooyk, Y., González-Cappa, S.M., Rabinovich, G.A.
Formato: JOUR
Materias:
CD4 antigen
galectin 1
interleukin 10
interleukin 17
interleukin 2 receptor alpha
transcription factor FOXP3
transforming growth factor beta1
gamma interferon
IDO1 protein, mouse
IL10 protein, mouse
indoleamine 2,3 dioxygenase
Pdcd1lg2 protein, mouse
programmed death 1 ligand 2
analysis of variance
animal cell
animal experiment
animal model
animal tissue
Article
CD8+ T lymphocyte
cell activation
cell differentiation
cell survival
cell viability
Chagas disease
confocal microscopy
controlled study
cytokine production
dendritic cell
disease predisposition
glycosylation
homeostasis
immunoblotting
immunogenicity
immunomodulation
lymphocyte proliferation
male
mononuclear cell
mouse
nonhuman
pathogen load
priority journal
protein analysis
protein binding
protein function
quantitative analysis
real time polymerase chain reaction
T lymphocyte
Th1 cell
Th17 cell
upregulation
animal
Bagg albino mouse
biosynthesis
C3H mouse
cytology
genetics
immunology
knockout mouse
lymph node
metabolism
mortality
parasite load
parasitology
regulatory T lymphocyte
Trypanosoma cruzi
Animals
CD8-Positive T-Lymphocytes
Chagas Disease
Dendritic Cells
Galectin 1
Indoleamine-Pyrrole 2,3,-Dioxygenase
Interferon-gamma
Interleukin-10
Lymph Nodes
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Knockout
Parasite Load
Programmed Cell Death 1 Ligand 2 Protein
T-Lymphocytes, Regulatory
Transforming Growth Factor beta1
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00221767_v195_n7_p3311_Poncini
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion. Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acute parasite infections is uncertain. In this study, we show that Gal-1 functions as a negative regulator to limit host-protective immunity following intradermal infection with Trypanosoma cruzi. Concomitant with the upregulation of immune inhibitory mediators, including IL-10, TGF-β1, IDO, and programmed death ligand 2, T. cruzi infection induced an early increase of Gal-1 expression in vivo. Compared to their wild-type (WT) counterpart, Gal-1-deficient (Lgals1-/-) mice exhibited reduced mortality and lower parasite load in muscle tissue. Resistance of Lgals1-/- mice to T. cruzi infection was associated with a failure in the activation of Gal-1-driven tolerogenic circuits, otherwise orchestrated by WT dendritic cells, leading to secondary dysfunction in the induction of CD4+CD25+Foxp3+ regulatory T cells. This effect was accompanied by an increased number of CD8+ T cells and higher frequency of IFN-γ-producing CD4+ T cells in muscle tissues and draining lymph nodes as well as reduced parasite burden in heart and hindlimb skeletal muscle. Moreover, dendritic cells lacking Gal-1 interrupted the Gal-1-mediated tolerogenic circuit and reinforced T cell-dependent anti-parasite immunity when adoptively transferred into WT mice. Thus, endogenous Gal-1 may influence T. cruzi infection by fueling tolerogenic circuits that hinder anti-parasite immunity.

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