Trypanosoma cruzi Calreticulin: Immune Evasion, Infectivity, and Tumorigenesis

Ramírez-Toloza, Galia; Sosoniuk-Roche, Eduardo; Valck, Carolina; Ferreira, Viviana P.; Ferreira, Arturo

doi:10.1016/j.pt.2020.01.007

Cited by 16 publications

(27 citation statements)

References 93 publications

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“…Thus, an important function of Calr in microorganisms is its capacity to bind C1, with consequent inhibition of the CP of C (4) and promotion of infectivity (1,4). More recently, these two important effects have also been described for Calr from a variety of protozoan and metazoan parasites (2). C1 binding allows the parasite to evade the C system and to promote engulfment of the parasite by mimicking a strategy used by apoptotic cells (12).…”

Section: Discussionmentioning

confidence: 99%

“…As reviewed elsewhere ( 2 ), in addition to their roles in C evasion and infectivity, TcCalr and its N-terminal domain are anti-angiogenic in several experimental set ups ( 97 – 99 ). The anti-tumor effect of T. cruzi infection has been fully reproduced by exogenously administrated rTcCalr ( 97 ) and reverted by polyclonal anti-rTcCalr F(ab') 2 antibodies ( 51 ).…”

Section: Other Tccalr Functions In the Host-parasite Interplaymentioning

confidence: 98%

“…Calr is a 46 kDa multifunctional protein, mainly located in the endoplasmic reticulum (ER) and highly conserved in all species, including plants and microorganisms (2,7,8). Calr is involved in Ca 2+ homeostasis and in other important functions inside and outside the cell, including: cardiogenesis, adipocyte differentiation, cellular stress responses, wound healing and immunity (9).…”

Section: C1 and Calreticulin Interaction Promotes Phagocytosismentioning

confidence: 99%

“…In nematodes Calr is also important in immune evasion (2). Necator americanus Calr (NaCalr) was first described as a hookworm allergen in infected patients (62).…”

Section: Calreticulin In Other Parasitic Infectionsmentioning

confidence: 99%

“…These issues are reviewed herein. TcCalr also participates in the control of angiogenesis and tumor growth, as reviewed elsewhere (2).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Other Tccalr Functions In the Host-parasite Interplaymentioning

confidence: 98%

Section: C1 and Calreticulin Interaction Promotes Phagocytosismentioning

confidence: 99%

“…In nematodes Calr is also important in immune evasion (2). Necator americanus Calr (NaCalr) was first described as a hookworm allergen in infected patients (62).…”

Section: Calreticulin In Other Parasitic Infectionsmentioning

confidence: 99%

“…These issues are reviewed herein. TcCalr also participates in the control of angiogenesis and tumor growth, as reviewed elsewhere (2).…”

Section: Introductionmentioning

confidence: 99%

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