The mucin-like glycoprotein super-family of Trypanosoma cruzi: structure and biological roles

Acosta-Serrano, Álvaro; Almeida, Igor C.; Freitas‐Junior, Lúcio H.; Yoshida, Nobuko; Schenkman, Sérgio

doi:10.1016/s0166-6851(01)00245-6

Cited by 178 publications

(160 citation statements)

References 65 publications

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“…We have not directly addressed the role of the glycosylphosphatidylinositol anchor, but the fact that AgC10 can be released by the enzyme phosphoinosytol-phospholipase C (PI-PLC) from the T. cruzi membrane and this supernatant was also suppressive (data not shown) is suggestive that this is not the case. In contrast with our results, others have shown that mucins from T. cruzi blood trypomastigotes are potent stimulators of macrophage proinflammatory activity [10]. It is noteworthy that AgC10 is present in the insect infective metacyclic forms and not in blood trypomastigotes [8], in sharp contrast with the immunostimulatory mucins present in blood trypomastigotes [14].…”

Section: Discussioncontrasting

confidence: 99%

“…cruzi mucins comprise a heterogeneous group of surface molecules required for the interaction with host cells during invasion [10]. Specifically, they play a role in invasion and survival inside host cells and in the modulation of macrophage functions [8,11].…”

Section: Introductionmentioning

confidence: 99%

“…and epimastigotes) that migrate in the 35-55 kDa range [8,12]. The other group includes mucins from tissuederived or blood trypomastigotes that migrate as a broad band of 60-200 kDa [10]. In all cases the protein portions of these mucins are encoded by a heterogeneous gene family [13], which appears to be differentially expressed in the different stages [14].…”

Section: Introductionmentioning

confidence: 99%

“…In all cases the protein portions of these mucins are encoded by a heterogeneous gene family [13], which appears to be differentially expressed in the different stages [14]. The carbohydrate structure and the lipid nature of their GPI anchors, which define their biological activity, also differ between the different stages [10].…”

Section: Introductionmentioning

confidence: 99%

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AgC10, a mucin from Trypanosoma cruzi, destabilizes TNF and cyclooxygenase‐2 mRNA by inhibiting mitogen‐activated protein kinase p38

Alcaide

Fresno

2004

Eur J Immunol

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Secretion of proinflammatory mediators by activated macrophages plays an important role in the immune response to Trypanosoma cruzi. We have previously reported that AgC10, a glycosylphosphatidylinositol-anchored mucin from T. cruzi, inhibits TNF secretion by activated macrophages (de Diego, J., Punzon, C., Duarte, M. and Fresno, M., Alteration of macrophage function by a Trypanosoma cruzi membrane mucin. J. Immunol. 1997. 159: 4983-4989). In this report we have further investigated the molecular mechanisms underlying this inhibition. AgC10 inhibited TNF, IL-10 and cyclooxygenase-2 (COX-2) synthesis by macrophages activated with LPS or LPS plus IFN-+ in a dose-dependent manner. AgC10 did not affect other aspects of macrophage activation induced by LPS, such as inducible nitric oxide synthase (iNOS) expression. AgC10 also had no effect on TNF or COX-2 transcription or the induction of their promoters but inhibited the stability of TNF and COX-2 mRNA, which are regulated post-transcriptionally by the mitogen-activated protein kinase (MAPK) p38 pathway. AgC10 was found to inhibit both the activation and the activity of p38 MAPK, since MAPK activated protein kinase-2 (MAPKAP-K2 or MK-2) phosphorylation was also strongly inhibited. This led to TNF and COX-2 mRNA destabilization. In contrast, AgC10 did not affect p38 activation induced by TNF. Furthermore, AgC10 inhibition must lie upstream in the MAPK activation pathway by LPS, since this mucin also inhibited extracellularly regulated kinase (ERK) and Jun kinase (JNK) activation.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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AgC10, a mucin from Trypanosoma cruzi, destabilizes TNF and cyclooxygenase‐2 mRNA by inhibiting mitogen‐activated protein kinase p38

Alcaide

Fresno

2004

Eur J Immunol

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“…Parasite maturation, which involves metacyclogenesis of T. cruzi from noninfective epimastigotes to infective trypomastigotes, occurs in the gut of the triatomine bugs and is an important step in the transmission of Chagas disease [34]. This maturation process is dependent on interactions between the surface epitopes of T. cruzi and the gut lumen of the insect vector [35] and would be the target of scFv effector activity.…”

Section: Single-chain Antibodiesmentioning

confidence: 99%

A Paratransgenic Strategy for the Control of Chagas Disease

Hurwitz

Fieck

Klein

et al. 2012

Psyche: A Journal of Entomology

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Chagas disease results from infection with the parasiteTrypanosoma cruzi. This disease remains a significant cause of morbidity and mortality in central and south America. Chagas disease now exists and is detected worldwide because of human migration. Control of Chagas disease has relied mainly on vector eradication however, the development of insect resistance to pesticides, coupled with cost and adverse health effects of insecticide treatments, has prompted our group to investigate novel methods of transmission control. Our laboratory has been instrumental in the development of the paratransgenic strategy to control vectorial transmission ofT. cruzi. In this paper, we discuss various components of the paratransgenic approach. Specifically, we describe classes of molecules that can serve as effectors, including antimicrobial peptides, endoglucanases, and highly specific single chain antibodies that target surface glycoprotein tags on the surface ofT. cruzi. Furthermore, we address evolving concepts related to field dispersal of engineered bacteria as part of the paratransgenic control strategy and attendant risk assessment evaluation.

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Conjugation Strategies Used for the Preparation of Carbohydrate‐Conjugate Vaccines

Hevey¹,

Ling²

2014

Chemistry of Bioconjugates

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The mucin-like glycoprotein super-family of Trypanosoma cruzi: structure and biological roles

Cited by 178 publications

References 65 publications

AgC10, a mucin from Trypanosoma cruzi, destabilizes TNF and cyclooxygenase‐2 mRNA by inhibiting mitogen‐activated protein kinase p38

AgC10, a mucin from Trypanosoma cruzi, destabilizes TNF and cyclooxygenase‐2 mRNA by inhibiting mitogen‐activated protein kinase p38

A Paratransgenic Strategy for the Control of Chagas Disease

Conjugation Strategies Used for the Preparation of Carbohydrate‐Conjugate Vaccines

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