Immune response to a major Trypanosoma cruzi antigen, cruzipain, is differentially modulated in C57BL/6 and BALB/c mice

Guiñazú, Natalia; Pellegrini, Andrea; Giordanengo, Laura; Aoki, María Pilar; Rivarola, Héctor Walter; Cano, Roxana Carolina; Rodrigues, Maurício M.; Gea, Susana

doi:10.1016/j.micinf.2004.07.010

Cited by 34 publications

(28 citation statements)

References 32 publications

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“…12 Consistent with our findings, Shi et al 13 found that T-helper subsets accounted for the extent of hepatic fibrosis when comparing C57BL/6 and BALB/c with their respective SCID phenotypes. They demonstrated that C57BL/6 developed significantly less hepatic fibrosis after CCL 4 -induced liver injury compared with the BALB/c with a similar degree of cellular necrosis.…”

Section: Discussionsupporting

confidence: 92%

Role of T Lymphocytes in Hypertension-Induced Cardiac Extracellular Matrix Remodeling

Horak

Larson

2006

Hypertension

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Abstract-Cardiac remodeling in response to pressure overload involves reorganization of the myocytes and extracellular matrix (ECM). Neurohormonal pathways have been described as effector pathways in left ventricular ECM reorganization in response to pressure overload; we now are assessing the role of the T lymphocyte in this process. Mice with defined differences in T-lymphocyte function (C57BL/6 SCID, C57BL/6 WT, and BALB/c) were treated with 50 mg/L of N G -nitro-L-arginine methyl ester in their drinking water for 30 days. The immune function of C57BL/6 WT mice was T-helper type 1 (TH1), BALB/c was TH2, and C57BL/6 SCID was null. The arterial blood pressure increased by 30% in all of the strains of mice. However, ventricular stiffness significantly decreased in the C57 SCID, significantly increased in the BALB/c, and did not change in the C57 WT. The characterization of matrix metalloproteinase induction and activation on day 30 was associated with T-lymphocyte function. The total cardiac fibrillar collagen, percentage of fibrillar collagen cross-linking, and the activity of the cross-linking enzyme lysyl oxidase-like-3 (LOXL-3) significantly decreased in the C57 SCID, significantly increased in the BALB/c, and did not change in the C57 WT. This study revealed that the LOXL-3 pathway, namely, gene expression, enzymatic activities, and LOXL-3-mediated collagen cross-linking, was associated with ventricular stiffness and incongruence with lymphocyte function. These data support the concept that the T lymphocytes may play a fundamental regulatory role in cardiac ECM composition through modulation of collagen synthesis, degradation, and cross-linking. Key Words: lymphocytes Ⅲ ventricular function Ⅲ collagen I n response to hypertension, the myocardium undergoes a series of changes, including adaptation of the extracellular matrix (ECM) composition. ECM remodeling leading to heart failure is characterized by disproportionate ECM fibrillar collagen synthesis and degradation 1 and collagen crosslinking by the enzyme lysyl oxidase (LOX). 2 These processes are mediated primarily by the cardiac fibroblast (CF), and, therefore, factors that modulate CF function will determine the nature of ECM remodeling in response to increased wall stress. It is understood that the CF function is under local as well as neurohormonal control. 3 We suggest that CF function is also affected by T-lymphocyte function.T lymphocytes participate in a regulatory role of virtually all immune responses and most nonlymphoid tissues. Several lines of evidence have shown that T lymphocytes are an essential component in the remodeling processes of noncardiac tissues, 4,5 and others have suggested a role in cardiovascular remodeling and heart failure. 2,6 The cytokine profile that has been used to describe subtypes of T-helper (CD4 ϩ ) lymphocytes is namely TH1 and TH2. 7 It is accepted that a pathological increase in neuroendocrine mediators and wall stress induce cardiac remodeling, and we proposed that, in a similar manner, a difference in TH1/TH2...

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Section: Discussionsupporting

confidence: 92%

Role of T Lymphocytes in Hypertension-Induced Cardiac Extracellular Matrix Remodeling

Horak

Larson

2006

Hypertension

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“…In this sense, previously we reported a preferential activation of the Th2 profile in BALB/c mice after immunization with Cz [17]. In contrast, B6 splenocytes showed a predominant induction of Th1 profile [18]. Results obtained in this work clearly show that the exogenous addition of IL-4 to activated B lymphocytes from B6 strain strongly protected them from cell death, whereas IL-4 added to the cultures of BALB/c mice did not modify the viability percentages at 24 h. It is, therefore, possible to speculate that IL-4 secreted by immune BALB/c B lymphocytes could contribute to the development of the Th2 profile and most likely to the increase in the B cell survival.…”

Section: Discussionmentioning

confidence: 65%

“…Interestingly, in human Chagas disease, antibodies specific to particular Cz epitopes were associated to severe cardiac damage [16,43]. Taken together, our results suggest that the higher viability and activation ability of B cells could improve the effectiveness of these cells as APCs, autoantibody producer and amplify and sustain the autoimmune response in Cz immune BALB/c mice [17,18,44].…”

Section: Discussionmentioning

confidence: 66%

“…Accumulating experimental evidence suggests that cruzipain (Cz), a major cysteine protease of the parasite [12,13], plays an important role in the disease's progression [14][15][16]. We previously reported that the immunization of BALB/c and C57BL/6 (B6) mice with Cz generated a heart autoimmune response and tissue damage only in BALB/c mice [17,18]. Interestingly, in BALB/c mice, we found an increased activation state of B cells as well as higher number of germinal center B cells and plasma cells than in B6 mice.…”

Section: Introductionmentioning

confidence: 99%

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Trypanosoma cruzi antigen immunization induces a higher B cell survival in BALB/c mice, a susceptible strain, compared to C57BL/6 B lymphocytes, a resistant strain to cardiac autoimmunity

Pellegrini

Silva

Arocena

et al. 2011

Med Microbiol Immunol

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Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and represents the most common infectious myocarditis worldwide. Autoimmunity is one of the mechanisms contributing to its pathogenesis. Although the cellular interactions that promote this autoimmune response are still poorly understood, several studies have demonstrated a key role for B lymphocytes since they secrete antibodies, cytokines and present antigens. Recently, we reported that immunization with cruzipain, an immunodominant T. cruzi antigen, induces a higher activation state in B cells from BALB/c mice (susceptible to cardiac autoimmunity) than B lymphocytes from C57BL/6 (a resistant strain). Here, we focused on the study of B cell survival in both mouse strains after cruzipain immunization and demonstrated an increased survival rate of B cells from BALB/c compared to C57BL/6 mice. This phenomenon was associated with a decreased expression of Fas/FasL and an increased expression of anti-apoptotic Bcl-2/Bcl-xL proteins. With the purpose to gain more knowledge about the mechanisms involved, we found that IL-4 produced by BALB/c B cells played a key role in the survival in an autocrine way whereas the addition of this bioactive cytokine rescued C57BL/6 B lymphocytes from apoptosis. Our findings suggest that in the absence of infection, both enhanced B cell activation induced by the immunization with a single parasite antigen and insufficient negative regulation can potentially contribute to autoimmunity seen in cruzipain immune BALB/c mice.

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“…Thus, it has been proposed that stress induces the suppression of cellular immunity without affecting the humoral immune response (Elenkov 2004). The Th1/Th2 balance has been related to differences in both innate and acquired immunity (Guinazu et al 2004).…”

Section: Cells (Dcs) In Vitromentioning

confidence: 99%

Stimulation of the histamine 4 receptor with 4-methylhistamine modulates the effects of chronic stress on the Th1/Th2 cytokine balance

et al. 2015

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Immune response to a major Trypanosoma cruzi antigen, cruzipain, is differentially modulated in C57BL/6 and BALB/c mice

Cited by 34 publications

References 32 publications

Role of T Lymphocytes in Hypertension-Induced Cardiac Extracellular Matrix Remodeling

Role of T Lymphocytes in Hypertension-Induced Cardiac Extracellular Matrix Remodeling

Trypanosoma cruzi antigen immunization induces a higher B cell survival in BALB/c mice, a susceptible strain, compared to C57BL/6 B lymphocytes, a resistant strain to cardiac autoimmunity

Stimulation of the histamine 4 receptor with 4-methylhistamine modulates the effects of chronic stress on the Th1/Th2 cytokine balance

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