Role of CCL3/MIP-1α and CCL5/RANTES during acute Trypanosoma cruzi infection in rats

Ester Roffê; Fabiano Oliveira; Adriano L.S. Souza; Vanessa Pinho; Danielle G. Souza; Patrícia R.S. Souza; Remo C. Russo; Helton C. Santiago; Álvaro J. Romanha; Herbert B. Tanowitz; Jesus G. Valenzuela; Mauro M. Teixeira

doi:10.1016/j.micinf.2010.04.011

Role of CCL3/MIP-1α and CCL5/RANTES during acute Trypanosoma cruzi infection in rats

Ester Roffê, Fabiano Oliveira, Adriano L.S. Souza, Vanessa Pinho, Danielle G. Souza, Patrícia R.S. Souza, Remo C. Russo, Helton C. Santiago, Álvaro J. Romanha, Herbert B. Tanowitz, Jesus G. Valenzuela, Mauro M. Teixeira

Pathology

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Chagas' disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-γ production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T. cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T. cruzi infection. These data reinforce the important role of chemokines during T. cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection.

Original language	English (US)
Pages (from-to)	669-676
Number of pages	8
Journal	Microbes and Infection
Volume	12
Issue number	8-9
DOIs	https://doi.org/10.1016/j.micinf.2010.04.011
State	Published - Aug 2010

Keywords

CCR5
Chemokines
Myocarditis
Trypanosoma cruzi

ASJC Scopus subject areas

Microbiology
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.micinf.2010.04.011

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@article{8d367fe0ac0a46418c532d51a8dfb962,

title = "Role of CCL3/MIP-1α and CCL5/RANTES during acute Trypanosoma cruzi infection in rats",

abstract = "Chagas' disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-γ production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T. cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T. cruzi infection. These data reinforce the important role of chemokines during T. cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection.",

keywords = "CCR5, Chemokines, Myocarditis, Trypanosoma cruzi",

author = "Ester Roff{\^e} and Fabiano Oliveira and Souza, {Adriano L.S.} and Vanessa Pinho and Souza, {Danielle G.} and Souza, {Patr{\'i}cia R.S.} and Russo, {Remo C.} and Santiago, {Helton C.} and Romanha, {{\'A}lvaro J.} and Tanowitz, {Herbert B.} and Valenzuela, {Jesus G.} and Teixeira, {Mauro M.}",

note = "Funding Information: This work was supported by Conselho Nacional de Pesquisa (CNPq, Brazil) , Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil) , Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior (CAPES, Brazil) , Fogarty International Research Collaboration Award (NIH/FIRCA, 1 R03-TW006857-01A1, USA), and NIH ( AI-076248 , USA).",

year = "2010",

month = aug,

doi = "10.1016/j.micinf.2010.04.011",

language = "English (US)",

volume = "12",

pages = "669--676",

journal = "Microbes and Infection",

issn = "1286-4579",

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number = "8-9",

}

TY - JOUR

T1 - Role of CCL3/MIP-1α and CCL5/RANTES during acute Trypanosoma cruzi infection in rats

AU - Roffê, Ester

AU - Oliveira, Fabiano

AU - Souza, Adriano L.S.

AU - Pinho, Vanessa

AU - Souza, Danielle G.

AU - Souza, Patrícia R.S.

AU - Russo, Remo C.

AU - Santiago, Helton C.

AU - Romanha, Álvaro J.

AU - Tanowitz, Herbert B.

AU - Valenzuela, Jesus G.

AU - Teixeira, Mauro M.

N1 - Funding Information: This work was supported by Conselho Nacional de Pesquisa (CNPq, Brazil) , Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil) , Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil) , Fogarty International Research Collaboration Award (NIH/FIRCA, 1 R03-TW006857-01A1, USA), and NIH ( AI-076248 , USA).

PY - 2010/8

Y1 - 2010/8

N2 - Chagas' disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-γ production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T. cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T. cruzi infection. These data reinforce the important role of chemokines during T. cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection.

AB - Chagas' disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-γ production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T. cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T. cruzi infection. These data reinforce the important role of chemokines during T. cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection.

KW - CCR5

KW - Chemokines

KW - Myocarditis

KW - Trypanosoma cruzi

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U2 - 10.1016/j.micinf.2010.04.011

DO - 10.1016/j.micinf.2010.04.011

M3 - Article

C2 - 20452453

AN - SCOPUS:77954627448

SN - 1286-4579

VL - 12

SP - 669

EP - 676

JO - Microbes and Infection

JF - Microbes and Infection

IS - 8-9

ER -

Role of CCL3/MIP-1α and CCL5/RANTES during acute Trypanosoma cruzi infection in rats

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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