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Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γ and CD40-CD40L Interactions

Published on Jan 1, 2014in Mediators of Inflammation3.545
· DOI :10.1155/2014/345659
Lúcia Cristina Jamli Abel2
Estimated H-index: 2
,
Ludmila Rodrigues Pinto Ferreira13
Estimated H-index: 13
+ 5 AuthorsEdecio Cunha-Neto38
Estimated H-index: 38
Abstract
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is characterized by immunopathology driven by IFN-γ secreting Th1-like T cells. T. cruzi has a thick coat of mucin-like glycoproteins covering its surface, which plays an important role in parasite invasion and host immunomodulation. It has been extensively described that T. cruzi or its products—like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI-mucins)—are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-γ primed murine macrophages. However, little is known about whether T. cruzi or GPI-mucins exert a similar action in human cells. We therefore decided to further investigate the in vitro cytokine production profile from human mononuclear cells from uninfected donors exposed to T. cruzi as well as tGPI-mucins. We observed that both living T. cruzi trypomastigotes and tGPI-mucins are potent inducers of IL-12 by human peripheral blood monocytes and this effect depends on CD40-CD40L interaction and IFN-γ. Our findings suggest that the polarized T1-type cytokine profile seen in T. cruzi infected patients might be a long-term effect of IL-12 production induced by lifelong exposure to T. cruzi tGPI-mucins.
  • References (44)
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References44
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#1Humberto Doriguêtto Gravina (UFMG: Universidade Federal de Minas Gerais)H-Index: 4
#2Lis Ribeiro do Valle Antonelli (FIOCRUZ: Oswaldo Cruz Foundation)H-Index: 23
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Pathogens express ligands for several TLRs that may play a role in the induction or control of the inflammatory response during infection. Concerning Trypanosoma cruzi, the agent of Chagas disease, we have previously characterized glycosylphosphatidylinositol (GPI) anchored mucin-like glycoproteins (tGPI-mucin) and unmethylated CpG DNA sequences as TLR2 and TLR9 agonists, respectively. Here we sought to determine how these TLRs may modulate the inflammatory response in the following cell populat...
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Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi. The immune system plays an important role in the reduction of parasite load, but may also contribute to the development of lesions observed during the chronic phase of the disease. We analyzed cytokines produced by inflammatory heart cells in 21 autopsy samples obtained from patients with Chagas' disease divided according to the presence or absence of heart failure (HF). Left ventricular sections were analyzed by immunohistoc...
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American trypanosomiasis is a parasitic disease caused by Trypanosoma cruzi. Involvement of the central nervous system may present as an acute meningoencephalitis, a chronic encephalopathy, or an embolic stroke from a cardiomyopathy. Diagnosis is made by demonstration of the parasite or T. cruzi- specific antibodies in cerebrospinal fluid. The parasite may also cause a peripheral neuropathy. Treatment is with nifurtimox or benzonidazole.
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Endemic Chagas disease has emerged as an important health disparity in the Americas. As a result, we face a situation in both Latin America and the US that bears a resemblance to the early years of the HIV/AIDS pandemic.
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#2Linda A. Jelicks (Yeshiva University)H-Index: 35
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Chagas disease, a neglected tropical disease, has recently caught the attention of the medical community outside the endemic countries, particularly those involved in cardiovascular medicine and surgery. Carlos Chagas, the famous Brazilian physician-scientist, discovered the protozoan parasite Trypanosoma cruzi as well as the clinical manifestations it causes. Interestingly, it has been shown that Chagas disease was present in South America long before it was discovered by Chagas in 1909. Paleop...
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Persistent pulmonary infection with Cryptococcus neoformans in C57BL/6 mice results in chronic inflammation that is characterized by an injurious Th2 immune response. In this study, we performed a comparative analysis of cryptococcal infection in wild-type versus CD40-deficient mice (in a C57BL/6 genetic background) to define two important roles of CD40 in the modulation of fungal clearance as well as Th2-mediated immunopathology. First, CD40 promoted microanatomic containment of the organism wi...
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#1Claudio R. F. Marinho (USP: University of São Paulo)H-Index: 20
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The physiopathology of Chagas' disease has been largely defined in murine infections with virulent strains which partially represent parasite diversity. This report reviews our studies with Sylvio X10/4 parasites, a Trypanosoma cruzi clone that induces no acute phase but in C3H/He mice leads to chronic myocarditis resembling the human disease.
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#1Angelina M. Bilate (NYU: New York University)H-Index: 17
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Chagas disease continues to be a significant public health problem, as ca. 10 million people are still infected with T. cruzi in Latin America. Decades after primary infection, 30% of individuals can develop a form of chronic inflammatory cardiomyopathy known as Chagas disease cardiomyopathy (CCC). Data from both murine models and human studies support the view that an autoimmune response as well as a parasite-driven immune response involving inflammatory cytokines and chemokines may both play a...
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#1Ricardo T. Gazzinelli (FIOCRUZ: Oswaldo Cruz Foundation)H-Index: 71
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Toll-like receptors (TLRs) have emerged as a major receptor family involved in non-self recognition. They have a vital role in triggering innate immunity and orchestrate the acquired immune response during bacterial and viral infection. However, the role of TLRs during infection with protozoan pathogens is less clear. Nevertheless, our understanding of how these parasitic microorganisms engage the host TLR signalling system has now entered a phase of rapid expansion. This Review describes recent...
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#1Leonardo Marques da Fonseca (UFRJ: Federal University of Rio de Janeiro)H-Index: 6
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The last decades have produced a plethora of evidence on the role of glycans, from cell adhesion to signaling pathways. Much of that information pertains to their role on the immune system and their importance on the surface of many human pathogens. A clear example of this is the flagellated protozoan Trypanosoma cruzi, which displays on its surface a great variety of glycoconjugates, including O-glycosylated mucin-like glycoproteins, as well as multiple glycan-binding proteins belonging to the t...
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