Chagas disease: Immunology of the disease at a glance

Cristovão-Silva, Ana Catarina; Castro, Maria Carolina Accioly Brelaz de; Hernandes, Marcelo Zaldini; Pereira, Valéria Rêgo Alves

doi:10.1016/j.cytogfr.2021.10.001

Cited by 24 publications

(23 citation statements)

References 98 publications

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“…Most individuals evolve to a chronic asymptomatic infection with low parasitism, but 30%-40% either have or will develop cardiomyopathy, digestive megasyndromes, or both (1). While effective innate and adaptive immunity promotes parasite control, imbalanced host immune responses to persistent infection are suggested to favor inflammation and the development of chronic Chagas pathology (2,3).…”

Section: Introductionmentioning

confidence: 99%

STING Signaling Drives Production of Innate Cytokines, Generation of CD8+ T Cells and Enhanced Protection Against Trypanosoma cruzi Infection

et al. 2022

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A variety of signaling pathways are involved in the induction of innate cytokines and CD8+ T cells, which are major players in protection against acute Trypanosoma cruzi infection. Previous data have demonstrated that a TBK-1/IRF3-dependent signaling pathway promotes IFN-β production in response to Trypanosoma cruzi, but the role for STING, a main interactor of these proteins, remained to be addressed. Here, we demonstrated that STING signaling is required for production of IFN-β, IL-6, and IL-12 in response to Trypanosoma cruzi infection and that STING absence negatively impacts activation of IRF-dependent pathways in response to the parasite. We reported no significant activation of IRF-dependent pathways and cytokine expression in RAW264.7 macrophages in response to heat-killed trypomastigotes. In addition, we showed that STING is essential for T. cruzi DNA-mediated induction of IFN-β, IL-6, and IL-12 gene expression in RAW264.7 macrophages. We demonstrated that STING-knockout mice have significantly higher parasitemia from days 5 to 8 of infection and higher heart parasitism at day 13 after infection. Although we observed similar heart inflammatory infiltrates at day 13 after infection, IFN-β, IL-12, CXCL9, IFN-γ, and perforin gene expression were lower in the absence of STING. We also showed an inverse correlation between parasite DNA and the expression of CXCL9, IFN-γ, and perforin genes in the hearts of infected animals at day 13 after infection. Finally, we reported that STING signaling is required for splenic IFN-β and IL-6 expression early after infection and that STING deficiency results in lower numbers of splenic parasite-specific IFN-γ and IFN-γ/perforin-producing CD8+ T cells, indicating a pivotal role for STING signaling in immunity to Trypanosoma cruzi.

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Section: Introductionmentioning

confidence: 99%

STING Signaling Drives Production of Innate Cytokines, Generation of CD8+ T Cells and Enhanced Protection Against Trypanosoma cruzi Infection

et al. 2022

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“…Algunos estudios con pacientes en la fase aguda señalan en esta etapa un aumento de las citocinas proinflamatorias involucradas en la resistencia a la infección por T. cruzi, como IFN-γ, TNF-α e IL-6. En contraste, la respuesta tipo Th2, con niveles aumentados de IL-4, se le relaciona con la susceptibilidad a la enfermedad (Cristovao-Silva et al, 2021).…”

Section: Efecto De T Cruzi En El Hospederounclassified

“…La transialidasa, es un factor de virulencia, que limita la respuesta proinflamatoria durante la presentación de antígenos y estimula la respuesta antiinflamatoria mediante la producción de IL-10, favorece la infección y la presencia del parásito en los tejidos (Freire-de-Lima, Fonseca, Oeltmann, Mendonça-Previato & Previato, 2015). Se ha demostrado que las mucinas protegen a T. cruzi de la acción de los anticuerpos y evitan la activación de los linfocitos T (Boscardin et al, 2010;Cristovao-Silva et al, 2021).…”

Section: Efecto De T Cruzi En El Hospederounclassified

Enfermedad de Chagas: biología y transmisión de Trypanosoma cruzi

et al. 2022

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En 1909, Carlos Justiniano Chagas describió por primera vez las manifestaciones clínicas de la enfermedad de Chagas. El parásito hemoflagelado Trypanosoma cruzi (agente) se caracteriza por la presencia de un flagelo, y en su citoplasma presenta organelos como el citostoma, los glicosomas, los reservosomas y un núcleo. El ciclo de vida de T. cruzi se inicia cuando el vector defeca sobre la piel del hospedero sus heces contienen tripomastigotes metacíclicos, que infectan las células del vertebrado. Los vectores de esta enfermedad pertenecen a la Subfamilia Triatominae, insectos hematófagos, nocturnos y con la capacidad de localizar a sus hospederos mediante la detección del calor. T. cruzi tiene efectos en la biología del insecto triatomino, en su comportamiento, en el funcionamiento del intestino, su sistema inmunológico y la microbiota asociada. En el hospedero mamífero, el parásito activa la respuesta inmune innata, y las citocinas tienen un papel clave para controlar la infección o bien evolucionar a la cronicidad. T. cruzi presenta una amplia diversidad genética, y bajo condiciones de laboratorio se han demostrado sus diferentes grados de virulencia y tropismo hacia los órganos blanco; sin embargo, no existe una asociación clara entre las cepas y el comportamiento clínico de la enfermedad. Esta revisión aborda la historia del descubrimiento de la enfermedad de Chagas y discute aspectos recientes sobre la biología de T. cruzi para comprender la dinámica de su transmisión.

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“…A successful control of the acute phase is engendered by macrophages producing IL-2, NO, CXCL9 and CXCL10, lymphocytes producing TNF, IFN-γ and IL-17, and dendritic cells producing IL-12 and TNF. The indeterminate form of the chronic phase is characterized by the low levels of IFN-γ and TNF, and adequate levels of IL-10 and IL-17, while the cardiac form of the chronic phase presents high levels of IFN-γ, TNF, IL-1β and TGF-β, and low IL-18 levels [22]. Figure 1 shows the steps where TGF-β is possibly involved, some of them also possibly influenced by one or more selenoproteins, and then depending on adequate Se intake and bioavailability.…”

Section: Chagas Disease Physiopathology: Complex and Multi-determinat...mentioning

confidence: 99%

“…mechanisms undergoing CCC pathogenesis (Figure 1): (1) a direct heart cell damage caused by parasite infection as nests that slowly but not synchronically disrupts the myocardium; (2) direct damage caused by focal CD8-driven infiltration with myocytolysis and muscle cell tissue substitution by focal fibrosis; (3) a neurogenic disbalance caused by excessive parasympathetic stimulation through neurotransmitter agonist action of muscarinic-like antibodies produced by T. cruzi-infected persons; and (4) endothelial disfunction with microvascular compromise, microthrombi and focal ischemia. A recent review of CD immunology summarizes the relevance of the immune system both to control the infection and drive it into a benign chronic indeterminate phase, or to foster and sustain chronic inflammation that leads to CCC pathogenesis [22]. A successful control of the acute phase is engendered by macrophages producing IL-2, NO, CXCL9 and CXCL10, lymphocytes producing TNF, IFN-γ and IL-17, and dendritic cells producing IL-12 and TNF.…”

Section: Chagas Disease Physiopathology: Complex and Multi-determinat...mentioning

confidence: 99%

Selenium, TGF-Beta and Infectious Endemic Cardiopathy: Lessons from Benchwork to Clinical Application in Chagas Disease

et al. 2022

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For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function. Starting from the main questions “Is Se deficiency related to heart inflammation and arrhythmogenesis in CCC?” and “Could Se be recommended as a therapeutic strategy for CCC?”, we show evidence implicating the complex and multidetermined CCC physiopathology, discussing its possible interplays with the multifunctional cytokine TGF-β as regulators of immune response and fibrosis. We present two new proposals to face this global public health challenge in vulnerable populations affected by this parasitic disease: fibrosis modulation mediated by TGF-β pathways and the possible use of selenoproteins as antioxidants regulating the increased reactive oxygen stress present in CCC inflammatory environments. We assess the opportunity to consider the beneficial effects of Se in preventing heart failure as a concept to be applied for CCC patients.

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Chagas disease: Immunology of the disease at a glance

Cited by 24 publications

References 98 publications

STING Signaling Drives Production of Innate Cytokines, Generation of CD8+ T Cells and Enhanced Protection Against Trypanosoma cruzi Infection

STING Signaling Drives Production of Innate Cytokines, Generation of CD8+ T Cells and Enhanced Protection Against Trypanosoma cruzi Infection

Enfermedad de Chagas: biología y transmisión de Trypanosoma cruzi

Selenium, TGF-Beta and Infectious Endemic Cardiopathy: Lessons from Benchwork to Clinical Application in Chagas Disease

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