The Targets of the Lytic Antibody Response against Trypanosoma cruzi

Krautz, Greice M.; Kissinger, Jessica C.; Krettli, Antoniana U.

doi:10.1016/s0169-4758(99)01581-1

Cited by 65 publications

(39 citation statements)

References 30 publications

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“…Therefore, differently from other T. cruzi complement regulators already described, TcCRT acts at the earliest stage of complement activation. Thus, we provide in this work experimental evidence showing that TcCRT, by virtue of its capacity to bind and inhibit the function of C1q, may contribute to the well-known (48) inability of the classical pathway to play a preponderant role in the defense against this parasite.…”

Section: Discussionmentioning

confidence: 77%

“…Complement-mediated lysis of trypomastigotes in vitro requires an intact alternative pathway because serum depletion of factor B and P completely abrogates lysis of trypomastigotes precoated with IgG (54,55). The classical pathway, although unable to efficiently lyse trypomastigotes on its own, serves an enhancing effect on the amplifying properties of the alternative pathway (48). This impairment of the classical pathway suggests the importance of exploring the existence of other parasite complement regulatory proteins.…”

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confidence: 99%

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The Classical Activation Pathway of the Human Complement System Is Specifically Inhibited by Calreticulin from Trypanosoma cruzi

Ferreira¹,

Valck²,

Sánchez

et al. 2004

The Journal of Immunology

124

141

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The high resistance of Trypanosoma cruzi trypomastigotes, the causal agent of Chagas’ disease, to complement involves several parasite strategies. In these in vitro studies, we show that T. cruzi calreticulin (TcCRT) and two subfragments thereof (TcCRT S and TcCRT R domains) bind specifically to recognition subcomponents of the classical and lectin activation pathways (i.e., to collagenous tails of C1q and to mannan-binding lectin) of the human complement system. As a consequence of this binding, specific functional inhibition of the classical pathway and impaired mannan-binding lectin to mannose were observed. By flow cytometry, TcCRT was detected on the surface of viable trypomastigotes and, by confocal microscopy, colocalization of human C1q with surface TcCRT of infective trypomastigotes was visualized. Taken together, these findings imply that TcCRT may be a critical factor contributing to the ability of trypomastigotes to interfere at the earliest stages of complement activation.

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Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

The Classical Activation Pathway of the Human Complement System Is Specifically Inhibited by Calreticulin from Trypanosoma cruzi

Ferreira¹,

Valck²,

Sánchez

et al. 2004

The Journal of Immunology

124

141

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“…16 Tc24 is a calcium-acyl switch protein localized to the flagellar pocket of the parasite, and is expressed in all developmental stages of T. cruzi. 17 There is greater than 97% sequence conservation in Tc24 between the T. cruzi strains. 18 Early studies in mice have shown that prophylactic immunization with Tc24 is protective in T. cruzi infection.…”

Section: Introductionmentioning

confidence: 99%

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

Barry

Wang

Jones

et al. 2016

Human Vaccines & Immunotherapeutics

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Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust T H 1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a T H 1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNg-producing splenocytes, IgG2a titers, and proliferative capacity of CD8 C T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system.

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“…The mechanism of trypomastigote lysis in the CoML test is through the alternative pathway of complement activation, as summarized in Fig. 3, further discussed below and as previously reviewed (Krautz et al 2000). The susceptibility of T. cruzi trypomastigotes to complement lysis needs to be tested each time after their isolation (from immunosuppressed mice or from cell cultures); only suspensions totally refractory to direct complement lysis are useful for the CoML test.…”

Section: Resultsmentioning

confidence: 99%

The utility of anti-trypomastigote lytic antibodies for determining cure of Trypanosoma cruzi infections in treated patients: an overview and perspectives

Krettli

2009

Mem. Inst. Oswaldo Cruz

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The Targets of the Lytic Antibody Response against Trypanosoma cruzi

Cited by 65 publications

References 30 publications

The Classical Activation Pathway of the Human Complement System Is Specifically Inhibited by Calreticulin from Trypanosoma cruzi

The Classical Activation Pathway of the Human Complement System Is Specifically Inhibited by Calreticulin from Trypanosoma cruzi

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

The utility of anti-trypomastigote lytic antibodies for determining cure of Trypanosoma cruzi infections in treated patients: an overview and perspectives

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