Trypanosoma cruzi-elicited CD8+ T cell-mediated myocarditis: chemokine receptors and adhesion molecules as potential therapeutic targets to control chronic inflammation?

Lannes-Vieira, Joseli

doi:10.1590/s0074-02762003000300002

Cited by 26 publications

(29 citation statements)

References 35 publications

(45 reference statements)

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“…11 These results led us to consider that CC chemokines, mainly CCL5/RANTES and CCL3/MIP-1␣, and the CC chemokine receptor CCR5 could be involved in the immunopathogenesis of T cruzi-triggered myocarditis. 9,12 Herein, we evaluated the expression of CCR5 on heartinfiltrating and peripheral blood leukocytes of T cruziinfected mice and used the N-terminal-methionylated RAN-TES (Met-RANTES), a selective CCR1 and CCR5 antagonist, 13 to modulate the early phase of T cruzi-elicited myocarditis. Female C3H/HeJ (H-2 k ) mice 5 to 7 weeks old obtained from the animal facilities of the Oswaldo Cruz Foundation (Rio de Janeiro, Brazil) were maintained under standard conditions and treated according to institutional guidelines regarding ethics of animal use of the Oswaldo Cruz Foundation.…”

Section: See P 1341mentioning

confidence: 99%

Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) Antagonist (Met-RANTES) Controls the Early Phase of Trypanosoma cruzi –Elicited Myocarditis

et al. 2004

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Background-Comprehension of the pathogenesis of Trypanosoma cruzi-elicited myocarditis is crucial to delineate strategies aimed at ameliorating the inflammation associated with heart dysfunction. The augmented expression of CC chemokines, especially CCL5/RANTES and CCL3/MIP-1␣, in the hearts of infected mice suggests a role for CC chemokines and their receptors in the pathogenesis of T cruzi-elicited myocarditis. Methods and Results-We report that during the early phase of infection in C3H/HeJ mice infected with 100 blood trypomastigotes of T cruzi, most of the inflammatory cells invading the heart tissue were CD8 ϩ cells and expressed CCR5, a CCL5/RANTES, and CCL3/MIP1-␣ receptor. Furthermore, peripheral blood CD8 ϩ T lymphocytes displayed increased expression of CCR5. These findings led us to use Met-RANTES, a selective CCR1 and CCR5 antagonist, to modulate the acute T cruzi-elicited myocarditis. Met-RANTES treatment did not interfere with parasitism but significantly decreased the numbers of CD4 ϩ and CD8 ϩ T cells, CCR5 ϩ , and interleukin-4 ϩ cells invading the heart, paralleling the diminished deposition of fibronectin. Moreover, Met-RANTES treatment resulted in increased survival of infected animals, compared with saline treatment. Conclusions-These results indicate that the massive influx of CCR5ϩ cells into cardiac tissue is not crucial for cell-mediated anti-T cruzi immunity but appears to be critical for pathogenesis of T cruzi-elicited myocarditis. Thus, CC chemokine receptors might become an attractive therapeutic target for further evaluation during T cruzi infection.

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Section: See P 1341mentioning

confidence: 99%

Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) Antagonist (Met-RANTES) Controls the Early Phase of Trypanosoma cruzi –Elicited Myocarditis

et al. 2004

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“…These observations led us to believe that the altered function in the heart from chronic chagasic patients is a consequence of the myocarditis elicited during the acute phase of infection. Thus, the elucidation of the molecules that control the initial recruitment of leukocytes and the intensity of the myocarditis in T. cruzi-infected hosts may represent an important step to elaborate new strategies for therapeutic intervention in the chagasic cardiopathy (4,5).…”

Section: O Ne Of the Hallmarks Of Infection With Trypanosoma Cruzimentioning

confidence: 99%

“…Hence, IFN-␥-deficient animals display less pronounced myocarditis during the acute phase of infection with T. cruzi (9,25). This proinflammatory activity of IFN-␥ is associated with its ability to promote the local production of certain chemokines, such as CCL5/RANTES, CXCL9/monokine induced by IFN-␥ (MIG), and CXCL10/IFN-␣-inducible protein 10 (IP-10), which are important in mediating the migration of activated CD4 ϩ and CD8 ϩ ␣␤ T lymphocytes (5,13,14,25). In T. cruzi-infected animals, expression of cellular adhesion molecules (CAMs) such as ICAM-1 and VCAM-1 is induced in the cardiac tissue, whereas a high percentage of peripheral blood T lymphocytes become highly positive for LFA-1, ICAM-1, and VLA-4 during the early acute and chronic phase (14,26,27).…”

Section: O Ne Of the Hallmarks Of Infection With Trypanosoma Cruzimentioning

confidence: 99%

Intercellular Adhesion Molecule 1 Deficiency Leads to Impaired Recruitment of T Lymphocytes and Enhanced Host Susceptibility to Infection withTrypanosoma cruzi

Michailowsky

Celes

Marino

et al. 2004

The Journal of Immunology

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In this study, we investigated the involvement of Th1 cytokines in the expression of cell adhesion molecules (CAM) and recruitment of inflammatory cells to the heart of mice infected with Trypanosoma cruzi. Our results show that endogenously produced IFN-γ is essential to induce optimal expression of VCAM-1 and ICAM-1 on the cardiac vascular endothelium of infected mice. Furthermore, the influx of inflammatory cells into the cardiac tissue was impaired in Th1 cytokine-deficient infected mice, paralleling the intensity of VCAM-1 and ICAM-1 expression on the vascular endothelium. Consistent with the importance of ICAM-1 in host resistance, ICAM-1 knockout (KO) mice were highly susceptible to T. cruzi infection, as assessed by mortality rate, parasitemia, and heart tissue parasitism. The enhanced parasitism was associated with a decrease in the numbers of CD4+ and CD8+ T lymphocytes in the heart tissue of ICAM-1 KO mice. Additionally, ICAM-1 KO mice mounted an unimpaired IFN-γ response and IFN-γ-dependent production of reactive nitrogen intermediates and parasite- specific IgG2a. Supporting the participation of ICAM-1 in cell migration during T. cruzi infection, the entrance of adoptively transferred PBL from T. cruzi-infected wild-type C57BL/6 mice into the cardiac tissue of ICAM-1 KO mice was significantly abrogated. Therefore, we favor the hypothesis that ICAM-1 plays a crucial role in T lymphocyte recruitment to the cardiac tissue and host susceptibility during T. cruzi infection.

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“…The IFN-γ and TNF-α play a major role in modulating chemokine expression and, consequently, the chemokine-mediated leukocyte influx (Aliberti et al 2001, Lannes-Vieira 2003.The decrease in the numbers of Th2 + cells could be the result of the differential expression of CCR5 high by Th1 and CCR5 low by Th2 (Loetscher et al 1998). It is possible that the Th2 cell population (CCR5 low ) could be blocked by Met-RANTES first.…”

mentioning

confidence: 99%

CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi-elicited myocarditis

Marino

Silva

Santos

et al. 2005

Mem. Inst. Oswaldo Cruz

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Trypanosoma cruzi-elicited CD8+ T cell-mediated myocarditis: chemokine receptors and adhesion molecules as potential therapeutic targets to control chronic inflammation?

Abstract: In Chagas disease, during the acute phase, the establishment of inflammatory processes is crucial for

Cited by 26 publications

References 35 publications

Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) Antagonist (Met-RANTES) Controls the Early Phase of Trypanosoma cruzi –Elicited Myocarditis

Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) Antagonist (Met-RANTES) Controls the Early Phase of Trypanosoma cruzi –Elicited Myocarditis

Intercellular Adhesion Molecule 1 Deficiency Leads to Impaired Recruitment of T Lymphocytes and Enhanced Host Susceptibility to Infection withTrypanosoma cruzi

CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi-elicited myocarditis

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