Effects of Interleukin-4 Deprivation and Treatment on Resistance to<i>Trypanosoma cruzi</i>

Abrahamsohn, Ises A.; Silva, Ana Paula Galvão da; Coffman, Robert L.

doi:10.1128/iai.68.4.1975-1979.2000

Cited by 32 publications

(26 citation statements)

References 17 publications

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“…Even more interestingly, C57BL/6, but not BALB/c mice, showed an efficient clearance of heart parasites by day 17 post-infection (figure 1C top). These differences in parasite load and control in the heart may explain the differences in survival between these mouse strains, which agrees with previous results indicating that C57BL/6 are more resistant than BALB/c to infection with the Y parasite strain [24].…”

Section: Resultssupporting

confidence: 92%

Analysis of the Dynamics of Infiltrating CD4+ T Cell Subsets in the Heart during Experimental Trypanosoma cruzi Infection

et al. 2013

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Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects several million people in Latin America. Myocarditis, observed during both the acute and chronic phases of the disease, is characterized by an inﬂammatory mononuclear cell infiltrate that includes CD4+ T cells. It is known that Th1 cytokines help to control infection. The role that Treg and Th17 cells may play in disease outcome, however, has not been completely elucidated. We performed a comparative study of the dynamics of CD4+ T cell subsets after infection with the T. cruzi Y strain during both the acute and chronic phases of the disease using susceptible BALB/c and non-susceptible C57BL/6 mice infected with high or low parasite inocula. During the acute phase, infected C57BL/6 mice showed high levels of CD4+ T cell infiltration and expression of Th1 cytokines in the heart associated with the presence of Treg cells. In contrast, infected BALB/c mice had a high heart parasite burden, low heart CD4+ T cell infiltration and low levels of Th1 and inflammatory cytokines, but with an increased presence of Th17 cells. Moreover, an increase in the expression of IL-6 in susceptible mice was associated with lethality upon infection with a high parasite load. Chronically infected BALB/c mice continued to present higher parasite burdens than C57BL/6 mice and also higher levels of IFN-γ, TNF, IL-10 and TGF-β. Thus, the regulation of the Th1 response by Treg cells in the acute phase may play a protective role in non-susceptible mice irrespective of parasite numbers. On the other hand, Th17 cells may protect susceptible mice at low levels of infection, but could, in association with IL-6, be pathogenic at high parasite loads.

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Section: Resultssupporting

confidence: 92%

Analysis of the Dynamics of Infiltrating CD4+ T Cell Subsets in the Heart during Experimental Trypanosoma cruzi Infection

et al. 2013

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“…This is consistent with a previous study where neutralization of IL-4 led to the decrease of parasitemia in mice infected with TulahueÂ n or RA strains of T. cruzi (Petray et al 1993). In contrast to these ®ndings, in mice infected with CA-1 or Y strain, anti-IL-4 mAb treatment showed no eect on parasitemia (Petray et al 1993;Abrahamsohn et al 2000). This contradiction is attributable to the dierences in the strains of T. cruzi.…”

Section: Discussioncontrasting

confidence: 51%

IL-4 reduces resistance of mice to Trypanosoma cruzi infection

Hiyama¹,

Hamano²,

Nakamura

et al. 2001

Parasitol Res

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The role of IL-4 has often been studied, especially in the Leishmania major infection model, but not in Trypanosoma cruzi infection. In the present study, the role of IL-4 in host defense against infection with the Tulahuen strain of T. cruzi was examined by depleting IL-4 with an anti-IL-4 monoclonal antibody in vivo. In both IL-4 depleted and control C57BL/6 mice, the parasitemia showed peaks on the 21st day of infection. Both parasitemia and mortality were decreased in IL-4 depleted mice compared with control mice when IFN-gamma and nitric oxide productions were increased in IL-4 depleted mice compared with control mice. The mice treated with N-nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase, showed increased susceptibility to T. cruzi infection to the same level in both IL-4 depleted and control mice. Thus, it is suggested that endogenous IL-4 induces susceptibility to T. cruzi mainly by suppressing the production of IFN-gamma and nitric oxide, which has trypanocidal activity.

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“…On the other hand, immunization with MASPpep-KLH induced higher levels of proinflammatory cytokines, such as IFN- γ, IL-12, and IL-17, than those elicited by MASPpep-KLH/Al. Taken together, our results indicate that the MASP-pep-KLH vaccine induces a more balanced profile of anti-inflammatory and proinflammatory cytokines that are known to play an important role in protection against T. cruzi infection [22-28]. …”

Section: Resultsmentioning

confidence: 94%

“…Stimulation of selected proinflammatory and anti-inflammatory cytokines plays a crucial role in resistance against T. cruzi [22-27]. Therefore, we analyzed the cytokine profile of mice immunized with MASPpep-KLH or MASPpep-KLH/Al, aiming to understand why mice immunized with MASPpep-KLH/Al had much lower survival rate than animals immunized with MASPpep-KLH (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…IL-4 is a stimulating factor for the differentiation and proliferation of B cells [45], supporting the higher antibody production observed in the two MASPpep-KLH-immunized groups. Although IL-4 per se is not a major determinant of resistance to T. cruzi infection or disease outcome, when expressed together with IL-10 it is able to control myocarditis [22]. It has also been shown that when IL-4 is more dominant than IL-10, parasitemia is enhanced [23].…”

Section: Discussionmentioning

confidence: 99%

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A synthetic peptide from Trypanosoma cruzi mucin-like associated surface protein as candidate for a vaccine against Chagas disease

Serna

Lara

Rodrigues

et al. 2014

Vaccine

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Chagas disease, caused by Trypanosoma cruzi, is responsible for producing significant morbidity and mortality throughout Latin America. The disease has recently become a public health concern to nonendemic regions like the U.S. and Europe. Currently there are no fully effective drugs or vaccine available to treat the disease. The mucin-associated surface proteins (MASPs) are glycosylphosphatidylinositol (GPI)-anchored glycoproteins encoded by a multigene family with hundreds of members. MASPs are among the most abundant antigens found on the surface of the infective trypomastigote stage of T. cruzi, thus representing an attractive target for vaccine development. Here we used immunoinformatics to select a 20-mer peptide with several predicted overlapping B-cell, MHC-I, and MHC-II epitopes, from a MASP family member expressed on mammal-dwelling stages of T. cruzi. The synthetic MASP peptide conjugated to keyhole limpet hemocyanin (MASPpep-KLH) was tested in presence or not of an adjuvant (alum, Al) as a vaccine candidate in the C3H/HeNsd murine model of T. cruzi infection. In considerable contrast to the control groups receiving placebo, Al, or KLH alone or the group immunized with MASPpep-KLH/Al, the group immunized with MASPpep-KLH showed 86% survival rate after challenge with a highly lethal dose of trypomastigotes. As evaluated by quantitative real-time polymerase chain reaction, MASPpep-KLH-immunized animals had much lower parasite load in the heart, liver, and spleen than control animals. Moreover, protected animals produced trypanolytic, protective antibodies, and a cytokine profile conducive to resistance against parasite infection. Finally, in vivo depletion of either CD4+ or CD8+T cells indicated that the latter are critical for protection in mice immunized with MASPpep-KLH. In summary, this new peptide-based vaccine with overlapping B- and T-cell epitopes is able to control T. cruzi infection in mice by priming both humoral and cellular immunity.

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Effects of Interleukin-4 Deprivation and Treatment on Resistance toTrypanosoma cruzi

Cited by 32 publications

References 17 publications

Analysis of the Dynamics of Infiltrating CD4+ T Cell Subsets in the Heart during Experimental Trypanosoma cruzi Infection

Analysis of the Dynamics of Infiltrating CD4+ T Cell Subsets in the Heart during Experimental Trypanosoma cruzi Infection

IL-4 reduces resistance of mice to Trypanosoma cruzi infection

A synthetic peptide from Trypanosoma cruzi mucin-like associated surface protein as candidate for a vaccine against Chagas disease

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