Identification of membrane components of Tripanossoma cruzi Modulators of complement system

Kipnis, Thereza Liberman; Joiner, K A; Silva, W. Dias da; Rimoldi, M. T.; Hammer, Carl H.; Sher, Alan

doi:10.1590/s0074-02761988000500069

Cited by 8 publications

(8 citation statements)

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“…The complement system, as one of the first line of host defense, has been shown to be particularly important in the development as well as control of T. cruzi infection [4][5][6]. Mannose-binding lectin (MBL) is a recognition molecule of innate immunity which activates the lectin pathway of complement.…”

mentioning

confidence: 99%

High levels of mannose-binding lectin are associated with the risk of severe cardiomyopathy in chronic Chagas Disease

Luz

Miyazaki

Neto

et al. 2010

International Journal of Cardiology

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mentioning

confidence: 99%

High levels of mannose-binding lectin are associated with the risk of severe cardiomyopathy in chronic Chagas Disease

Luz

Miyazaki

Neto

et al. 2010

International Journal of Cardiology

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“…Several molecules present on the parasite have been identified as resistance mediators, at different levels of the C cascade. Moreover, trypomastigotes capture inhibitory host components, which are used to inhibit the C activation on the parasite surface, such as: plasma-membrane derived-vesicles (PMV) ( 25 , 26 ), T. cruzi trypomastigotes-decay accelerating factor (T-DAF) ( 27 , 28 ), T. cruzi C regulatory protein (CRP) ( 29 – 32 ); Factor H (FH) ( 33 ), gp58/68 ( 34 ), and C2 receptor inhibitor trispanning (CRIT) ( 21 , 35 ) ( Table 1 ). The molecular inhibitory mechanisms of these proteins are only partially known.…”

Section: Trypanosoma Cruzi Evades the Complement System: Thementioning

confidence: 99%

The Interactions of Parasite Calreticulin With Initial Complement Components: Consequences in Immunity and Virulence

et al. 2020

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Because of its capacity to increase a physiologic inflammatory response, to stimulate phagocytosis, to promote cell lysis and to enhance pathogen immunogenicity, the complement system is a crucial component of both the innate and adaptive immune responses. However, many infectious agents resist the activation of this system by expressing or secreting proteins with a role as complement regulatory, mainly inhibitory, proteins. Trypanosoma cruzi, the causal agent of Chagas disease, a reemerging microbial ailment, possesses several virulence factors with capacity to inhibit complement at different stages of activation. T. cruzi calreticulin (TcCalr) is a highly-conserved, endoplasmic reticulum-resident chaperone that the parasite translocates to the extracellular environment, where it exerts a variety of functions. Among these functions, TcCalr binds C1, MBL and ficolins, thus inhibiting the classical and lectin pathways of complement at their earliest stages of activation. Moreover, the TcCalr/C1 interaction also mediates infectivity by mimicking a strategy used by apoptotic cells for their removal. More recently, it has been determined that these Calr strategies are also used by a variety of other parasites. In addition, as reviewed elsewhere, TcCalr inhibits angiogenesis, promotes wound healing and reduces tumor growth. Complement C1 is also involved in some of these properties. Knowledge on the role of virulence factors, such as TcCalr, and their interactions with complement components in host-parasite interactions, may lead toward the description of new anti-parasite therapies and prophylaxis.

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“…Several molecules present on the parasite mediate resistance at different levels of the complement system cascade. In addition, trypomastigotes capture inhibitory host components, which are used to inhibit complement activation on the parasite surface, such as: PMV ( Figure 1A ) ( Cestari et al, 2012 ), TcCRT ( Figures 1B,C ) ( Ferreira et al, 2004 ), T. cruzi trypomastigote-decay accelerating factor (T-DAF) ( Figure 1D ) ( Kipnis et al, 1988 ; Tambourgi et al, 1993 ), T. cruzi complement regulatory protein (TcCRP) ( Figure 1E ) ( Norris et al, 1991 ; Norris and Schrimpf, 1994 ; Beucher et al, 2003 ); FH ( Figure 1F ) ( Schenkman et al, 1986 ), gp58/68 ( Figure 1G ) ( Fischer et al, 1988 ) and C2 receptor inhibitor trispanning (CRIT) ( Figure 1H ) ( Cestari Idos et al, 2008 ). The molecular inhibitory mechanisms of these proteins are only partially known for some of these molecules, but the central role is in the inhibition (decay) of C3 and/or C5 convertases.…”

Section: Complement Regulatory Proteins Expressed On T Crumentioning

confidence: 99%

“…Trypanosoma cruzi trypomastigotes (metacyclic, bloodstream and tissue culture-derived), but not epimastigotes, express a surface glycoprotein of 87–93 kDa, with decay accelerating activity, named trypomastigote-decay accelerating factor (T-DAF) ( Kipnis et al, 1988 ; Tambourgi et al, 1993 ). T-DAF interferes with the efficient assembly of the C3 and C5 convertases of both CP and AP ( Figure 1D ), and it is functionally analogous to human DAF ( Tambourgi et al, 1993 ).…”

Section: Complement Regulatory Proteins Expressed On T Crumentioning

confidence: 99%

Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin

Ramírez-Toloza

Ferreira

2017

Front. Microbiol.

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American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant. Thus T. cruzi susceptibility to complement varies depending on the parasite stage (amastigote, trypomastigotes or epimastigote) and on the T. cruzi strain. To avoid complement-mediated lysis, T. cruzi trypomastigotes express on the parasite surface a variety of complement regulatory proteins, such as glycoprotein 58/68 (gp58/68), T. cruzi complement regulatory protein (TcCRP), trypomastigote decay-accelerating factor (T-DAF), C2 receptor inhibitor trispanning (CRIT) and T. cruzi calreticulin (TcCRT). Alternatively, or concomitantly, the parasite captures components with complement regulatory activity from the host bloodstream, such as factor H (FH) and plasma membrane-derived vesicles (PMVs). All these proteins inhibit different steps of the classical (CP), alternative (AP) or lectin pathways (LP). Thus, TcCRP inhibits the CP C3 convertase assembling, gp58/68 inhibits the AP C3 convertase, T-DAF interferes with the CP and AP convertases assembling, TcCRT inhibits the CP and LP, CRIT confers ability to resist the CP and LP, FH is used by trypomastigotes to inhibit the AP convertases and PMVs inhibit the CP and LP C3 convertases. Many of these proteins have similar molecular inhibitory mechanisms. Our laboratory has contributed to elucidate the role of TcCRT in the host-parasite interplay. Thus, we have proposed that TcCRT is a pleiotropic molecule, present not only in the parasite endoplasmic reticulum, but also on the trypomastigote surface, participating in key processes to establish T. cruzi infection, such as inhibition of the complement system and serving as an important virulence factor. Additionally, TcCRT interaction with key complement components, participates as an anti-angiogenic and anti-tumor molecule, inhibiting at least in important part, tumor growth in infected animals.

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Identification of membrane components of Tripanossoma cruzi Modulators of complement system

Cited by 8 publications

References 0 publications

High levels of mannose-binding lectin are associated with the risk of severe cardiomyopathy in chronic Chagas Disease

High levels of mannose-binding lectin are associated with the risk of severe cardiomyopathy in chronic Chagas Disease

The Interactions of Parasite Calreticulin With Initial Complement Components: Consequences in Immunity and Virulence

Trypanosoma cruzi Evades the Complement System as an Efficient Strategy to Survive in the Mammalian Host: The Specific Roles of Host/Parasite Molecules and Trypanosoma cruzi Calreticulin

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