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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 Inflammation3.54
· DOI :10.1155/2014/345659
Lúcia Abel8
Estimated H-index: 8
,
Ludmila Rodrigues Pinto Ferreira12
Estimated H-index: 12
+ 5 AuthorsEdecio Cunha-Neto37
Estimated H-index: 37
Cite
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)
  • Citations (12)
Cite
References44
Newest
Published on May 1, 2013in PLOS ONE2.78
Humberto Doriguêtto Gravina4
Estimated H-index: 4
(UFMG: Universidade Federal de Minas Gerais),
Lis Ribeiro do Valle Antonelli21
Estimated H-index: 21
(FIOCRUZ: Oswaldo Cruz Foundation)
+ 1 AuthorsCatherine Ropert22
Estimated H-index: 22
(FIOCRUZ: Oswaldo Cruz Foundation)
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...
Published on Jun 1, 2012in Infectious Disease Clinics of North America4.76
Anis Rassi Junior30
Estimated H-index: 30
,
Joffre Marcondes de Rezende10
Estimated H-index: 10
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.
Published on May 29, 2012in PLOS Neglected Tropical Diseases4.49
Peter J. Hotez82
Estimated H-index: 82
(BCM: Baylor College of Medicine),
Eric Dumonteil38
Estimated H-index: 38
(UADY: Universidad Autónoma de Yucatán)
+ 7 AuthorsMaria Elena Bottazzi32
Estimated H-index: 32
(BCM: Baylor College of Medicine)
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.
Published on Jan 1, 2012in Clinical & Developmental Immunology
Denise Bertulucci Rocha Rodrigues13
Estimated H-index: 13
,
Marlene Antônia dos Reis22
Estimated H-index: 22
+ 4 AuthorsVirmondes Rodrigues13
Estimated H-index: 13
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...
Published on Jan 1, 2012in Cardiology in Review1.55
Fabiana S. Machado26
Estimated H-index: 26
(UFMG: Universidade Federal de Minas Gerais),
Linda A. Jelicks34
Estimated H-index: 34
(Yeshiva University)
+ 13 AuthorsAntonio Carlos Campos de Carvalho33
Estimated H-index: 33
(Yeshiva University)
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...
Published on Nov 1, 2010in American Journal of Pathology3.76
Gwo Hsiao Chen22
Estimated H-index: 22
(UM: University of Michigan),
John J. Osterholzer20
Estimated H-index: 20
(UM: University of Michigan)
+ 4 AuthorsGalen B. Toews79
Estimated H-index: 79
(UM: University of Michigan)
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...
Published on Nov 1, 2009in Microbes and Infection2.67
Claudio R. F. Marinho18
Estimated H-index: 18
(USP: University of São Paulo),
Luis N. Nuñez-Apaza1
Estimated H-index: 1
(USP: University of São Paulo)
+ 8 AuthorsMaria Regina D'Império Lima20
Estimated H-index: 20
(USP: University of São Paulo)
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.
Angelina M. Bilate18
Estimated H-index: 18
(NYU: New York University),
Edecio Cunha-Neto37
Estimated H-index: 37
(USP: University of São Paulo)
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...
Published on Dec 1, 2006in Nature Reviews Immunology44.02
Ricardo T. Gazzinelli68
Estimated H-index: 68
(FIOCRUZ: Oswaldo Cruz Foundation),
Eric Y. Denkers48
Estimated H-index: 48
(Cornell University)
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...
Published on Mar 1, 2006in Tropical Medicine & International Health2.42
Marta Maria Geraldes Teixeira34
Estimated H-index: 34
(USP: University of São Paulo),
Flávia Maia da Silva10
Estimated H-index: 10
(USP: University of São Paulo)
+ 6 AuthorsAnna Maria S. Stolf11
Estimated H-index: 11
(USP: University of São Paulo)
Summary Trypanosoma cruzi, the agent of Chagas disease, is genetically classified into two major evolutionarylineages, T. cruzi I and T. cruzi II. In Southern American Cone countries it is T cruzi II which causesmost cases of severe chronic Chagas disease. Contrary to this, we isolated T. cruzi I nested inendomyocardial biopsies of a chronic chagasic patient with end-stage heart failure. Our finding shouldalert clinicians to the possibility of severe Chagas disease in all regions where T. cruzi ci...
Cited By12
Newest
Published on Sep 1, 2019in International Immunopharmacology3.36
Srinivasa Reddy Bonam5
Estimated H-index: 5
(Indian Institute of Chemical Technology),
Debabrata Bhunia2
Estimated H-index: 2
(Indian Institute of Chemical Technology)
+ 3 AuthorsSampath Kumar Halmuthur Mahabalarao (Indian Institute of Chemical Technology)
Abstract A focused library of novel mannosylated glycophospholipids was synthesized employing imidate coupling and H-phosphate phosphorylation methods. All novel glycophospholipids were evaluated for their receptor interactions by molecular docking studies. Docking studies revealed dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) specific interaction of the glycophospholipid ligand P4 acts, which was further confirmed by in vitro DC-SIGN expression on mon...
Published on Feb 6, 2019in Frontiers in Immunology4.72
Leonardo Marques da Fonseca6
Estimated H-index: 6
(UFRJ: Federal University of Rio de Janeiro),
Kelli Monteiro da Costa3
Estimated H-index: 3
(UFRJ: Federal University of Rio de Janeiro)
+ 5 AuthorsLeonardo Freire-de-Lima14
Estimated H-index: 14
(UFRJ: Federal University of Rio de Janeiro)
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 is the flagellated protozoan Trypanosoma cruzi that display in its surface, including the O-linked mucin-like glycoproteins, as well as glycan-binding proteins belonging to the trans-sialidase (TS) family, which present active (aTS) an...
Published on Nov 7, 2018in Cells
Bruna F. Pinto1
Estimated H-index: 1
,
Nayara I. Medeiros5
Estimated H-index: 5
+ 4 AuthorsJuliana de Assis Silva Gomes18
Estimated H-index: 18
Chagas disease, caused by Trypanosoma cruzi, is a potentially life-threatening tropical disease endemic to Latin American countries that affects approximately 8 million people. In the chronic phase of the disease, individuals are classified as belonging to the indeterminate clinical form or to the cardiac and/or digestive forms when clinical symptoms are apparent. The relationship between monocytes and lymphocytes may be an important point to help clarify the complexity that surrounds the clinic...
Published on Mar 1, 2018
Marcos Lopez17
Estimated H-index: 17
(University of Valle),
Herbert B. Tanowitz53
Estimated H-index: 53
(Albert Einstein College of Medicine),
Shivali Gupta34
Estimated H-index: 34
(UTMB: University of Texas Medical Branch)
Purpose of Review Trypanosoma cruzi is the causative agent of Chagas disease. Decades after initial infection, ~ 30% of individuals can develop chronic chagasic cardiomyopathy. There are several proposed mechanisms for pathogenesis of Chagas disease, including parasite persistence, immune responses against parasite or self that continue in the heart, vascular compromise, and involvement of autonomic and central nervous system. Herein, we will focus on the significance of macrophages, mitochondri...
Published on Feb 16, 2018in Frontiers in Immunology4.72
Sue-jie Koo5
Estimated H-index: 5
(UTMB: University of Texas Medical Branch),
Bartosz Szczesny23
Estimated H-index: 23
(UTMB: University of Texas Medical Branch)
+ 2 AuthorsShivali Gupta34
Estimated H-index: 34
(UTMB: University of Texas Medical Branch)
Metabolism provides substrates for reactive oxygen species (ROS) and nitric oxide (NO) generation, which are a part of the macrophage (mφ) anti-microbial response. Mφs infected with Trypanosoma cruzi (Tc) produce insufficient levels of oxidative species and lower levels of glycolysis compared to classically-activated mφs. How mφs fail to elicit a potent ROS/NO response during infection and its link to glycolysis is unknown. Herein, we evaluated for ROS, NO, and cytokine production in the presenc...
Published on Nov 1, 2017in Experimental Parasitology1.72
Rafael Carvalho de Freitas2
Estimated H-index: 2
(UEL: Universidade Estadual de Londrina),
Sandra Cristina Heim Lonien2
Estimated H-index: 2
(UEL: Universidade Estadual de Londrina)
+ 8 AuthorsJuliano Bordignon16
Estimated H-index: 16
(FIOCRUZ: Oswaldo Cruz Foundation)
Abstract Cell invasion by Trypanosoma cruzi and its intracellular replication are essential for progression of the parasite life cycle and development of Chagas disease. Prostaglandin E2 (PGE 2 ) and other eicosanoids potently modulate host response and contribute to Chagas disease progression. In this study, we evaluated the effect of aspirin (ASA), a non-selective cyclooxygenase (COX) inhibitor on the T. cruzi invasion and its influence on nitric oxide and cytokine production in human monocyte...
Published on Aug 11, 2017in PLOS Neglected Tropical Diseases4.49
María de los Milagros Cámara1
Estimated H-index: 1
(Universidad Argentina de la Empresa),
Gaspar E. Cánepa6
Estimated H-index: 6
(CONICET: National Scientific and Technical Research Council)
+ 6 AuthorsCarlos A. Buscaglia24
Estimated H-index: 24
(CONICET: National Scientific and Technical Research Council)
Background TSSA (Trypomastigote Small Surface Antigen) is an antigenic, adhesion molecule displayed on the surface of Trypanosoma cruzi trypomastigotes. TSSA displays substantial sequence identity to members of the TcMUC gene family, which code for the trypomastigote mucins (tGPI-mucins). In addition, TSSA bears sequence polymorphisms among parasite strains; and two TSSA variants expressed as recombinant molecules (termed TSSA-CL and TSSA-Sy) were shown to exhibit contrasting features in their h...
Published on Jan 1, 2017
Carine Truyens27
Estimated H-index: 27
(ULB: Université libre de Bruxelles),
Yves Carlier38
Estimated H-index: 38
(Tulane University)
Abstract The immune response to T. cruzi infection is particularly complex due to the presence, in the host, of both extracellular and intracellular parasites (invading different cell types and tissues), therefore requiring different types of responses. This chapter reviews in depth the innate and adaptive immune mechanisms allowing the host to partially control acute infection, underlying recent advances on innate parasite recognition, and on how the key cytokines IFN-gamma and IL-17 are protec...
Published on Dec 21, 2016in The Journal of Infectious Diseases5.04
Ludmila Rodrigues Pinto Ferreira12
Estimated H-index: 12
,
Frederico Moraes Ferreira8
Estimated H-index: 8
+ 12 AuthorsMark Seielstad54
Estimated H-index: 54
(Systems Research Institute)
Published on Dec 1, 2016in Parasites & Vectors3.03
Cecilia Stahl Vieira4
Estimated H-index: 4
(FIOCRUZ: Oswaldo Cruz Foundation),
Peter J. Waniek10
Estimated H-index: 10
(FIOCRUZ: Oswaldo Cruz Foundation)
+ 3 AuthorsP. Azambuja31
Estimated H-index: 31
(FIOCRUZ: Oswaldo Cruz Foundation)
Background Rhodnius prolixus is a major vector of Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. In natural habitats, these insects are in contact with a variety of bacteria, fungi, virus and parasites that they acquire from both their environments and the blood of their hosts. Microorganism ingestion may trigger the synthesis of humoral immune factors, including antimicrobial peptides (AMPs). The objective of this study was to compare the expression levels of AMPs (d...
View next paperGlycoconjugates isolated from Trypanosoma cruzi but not from Leishmania species membranes trigger nitric oxide synthesis as well as microbicidal activity in IFN-gamma-primed macrophages.