Trypanosoma cruzi calreticulin inhibits the complement lectin pathway activation by direct interaction with L-Ficolin

Sosoniuk, Eduardo; Vallejos, Gerardo; Kenawy, Hany I.; Gaboriaud, Christine; Thielens, Nicole M.; Fujita, Teizo; Schwaeble, Wilhelm; Ferreira, Arturo; Valck, Carolina

doi:10.1016/j.molimm.2014.03.014

Cited by 46 publications

(50 citation statements)

References 44 publications

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“…It has been shown to be capable of binding different molecular pattern sensors, like C1q, mannose binding protein (MBP, also known as mannose binding lectin) (15) and L-ficolin (16). Therefore, it affects the first step on the classical and lectin complement activation pathways.…”

Section: Innate Immunitymentioning

confidence: 99%

The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

2018

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Trypanosoma cruzi interacts with the different arms of the innate and adaptive host's immune response in a very complex and flowery manner. The history of host-parasite co-evolution has provided this protozoan with means of resisting, escaping or subverting the mechanisms of immunity and establishing a chronic infection. Despite many decades of research on the subject, the infection remains incurable, and the factors that steer chronic Chagas disease from an asymptomatic state to clinical onset are still unclear. As the relationship between T. cruzi and the host immune system is intricate, so is the amount and diversity of scientific knowledge on the matter. Many of the mechanisms of immunity are fairly well understood, but unveiling the factors that lead each of these to success or failure, within the coordinated response as a whole, requires further research. The intention behind this Review is to compile the available information on the different aspects of the immune response, with an emphasis on those phenomena that have been studied and confirmed in the human host. For ease of comprehension, it has been subdivided in sections that cover the main humoral and cell-mediated components involved therein. However, we also intend to underline that these elements are not independent, but function intimately and concertedly. Here, we summarize years of investigation carried out to unravel the puzzling interplay between the host and the parasite.

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Section: Innate Immunitymentioning

confidence: 99%

The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

2018

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“…29 It is then possible that saliva, ejected at the bite site, contains molecules that inhibit the complement proteins present in the massive blood meal that floods the first part of the insect's digestive tract. We propose that CRT, a multifunctional molecule, known to be present in salivary gland extracts from insects 30,31 and to inhibit the complement system, 19,32,33 could be responsible at least partly, for this effect (A dynamic view of this functional perception is presented in Supplemental Video).…”

Section: Discussionmentioning

confidence: 99%

“…32 Resulting inhibition of the classical pathway of the complement system is detectable. 19,32,33,39 Based on this rationale, we asked whether this capacity was present in TiCRT.…”

Section: Discussionmentioning

confidence: 99%

Triatoma infestans Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts with the Host Complement System

Weinberger

Collazo

Aguillón

et al. 2017

The American Society of Tropical Medicine and Hygiene

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Abstract. Triatoma infestans is an important hematophagous vector of Chagas disease, a neglected chronic illness affecting approximately 6 million people in Latin America. Hematophagous insects possess several molecules in their saliva that counteract host defensive responses. Calreticulin (CRT), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. Human CRT (HuCRT) and Trypanosoma cruzi CRT (TcCRT) inhibit the classical pathway of complement activation, mainly by interacting through their central S domain with complement component C1. In previous studies, we have detected CRT in salivary gland extracts from T. infestans. We have called this molecule TiCRT. Given that the S domain is responsible for C1 binding, we have tested its role in the classical pathway of complement activation in vertebrate blood. We have cloned and characterized the complete nucleotide sequence of CRT from T. infestans, and expressed its S domain. As expected, this S domain binds to human C1 and, as a consequence, it inhibits the classical pathway of complement, at its earliest stage of activation, namely the generation of C4b. Possibly, the presence of TiCRT in the salivary gland represents an evolutionary adaptation in hematophagous insects to control a potential activation of complement proteins, present in the massive blood meal that they ingest, with deleterious consequences at least on the anterior digestive tract of these insects.

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“…While TcCRT prevented C1r 2 C1s 2 from binding C1q, it failed to displace C1r 2 C1s 2 in a preformed C1 complex and only blocked C1s cleavage of C4 in the context of C1 but not the isolated C1s enzyme (70). As with HAstV-1 Coat Protein, TcCRT was recently shown to also block LP activation (71). This observation further supports the concept of a partially overlapping mechanism by these otherwise distinct inhibitors.…”

Section: Disruption Of the C1 Complexmentioning

confidence: 99%

Novel Evasion Mechanisms of the Classical Complement Pathway

Garcia

Zwarthoff

Rooijakkers

et al. 2016

The Journal of Immunology

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Complement is a network of soluble and cell surface-associated proteins which gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of ‘non-self’ cells by one of three initiating mechanisms known as the classical, lectin, or alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. While many complement inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review we focus on several recent investigations which have revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules.

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Trypanosoma cruzi calreticulin inhibits the complement lectin pathway activation by direct interaction with L-Ficolin

Cited by 46 publications

References 44 publications

The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease

Triatoma infestans Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts with the Host Complement System

Novel Evasion Mechanisms of the Classical Complement Pathway

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