Mechanisms of complement lectin pathway activation and resistance by trypanosomatid parasites

Cestari, Igor; Evans-Osses, Ingrid; Schlapbach, Luregn J.; Messias-Reason, Iara; Ramirez, Marcel I.

doi:10.1016/j.molimm.2012.08.015

Cited by 40 publications

(47 citation statements)

References 63 publications

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“…Protein extracts of parasites were then subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis and after transferred to nitrocellulose membrane. The membrane was then incubated with monoclonal mouse anti‐human MBL (1:1000, Antibodyshop, Denmark) and secondly with goat anti‐mouse IgG conjugated with HRP (1:500) (Santa Cruz Biotech) as described elsewhere [21].…”

Section: Methodsmentioning

confidence: 99%

Differential ability to resist to complement lysis and invade host cells mediated by MBL in R4 and 860 strains of Trypanosoma cruzi

et al. 2014

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a b s t r a c tTo produce an infection Trypanosoma cruzi must evade lysis by the complement system. During early stages of infection, the lectin pathway plays an important role in host defense and can be activated by binding of mannan-binding lectin (MBL) to carbohydrates on the surface of pathogens. We hypothesized that MBL has a dual role during parasite-host cell interaction as lectin complement pathway activator and as binding molecule to invade the host cell. We used two polarized strains of T. cruzi, R4 (susceptible) and 860 (resistant) strains, to investigate the role of MBL in complementmediated lysis. Interestingly R4, but not 860 metacyclic strain, markedly increases the invasion of host cells, suggesting that MBL drives the invasion process while the parasite deactivates the Lectin complement pathway.

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Section: Methodsmentioning

confidence: 99%

Differential ability to resist to complement lysis and invade host cells mediated by MBL in R4 and 860 strains of Trypanosoma cruzi

et al. 2014

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“…The complement lectin pathway can be activated by Trypanosoma and Leishmania (Cestari et al 2013). MBL binds to glycosylated antigens on Trypanosoma cruzi, on the surface of metacyclic trypomastigotes, resulting in complement activation (Cestari Idos et al 2009).…”

Section: Interaction Of Collectins With Protozoal and Helminth Pathogensmentioning

confidence: 99%

Collectins: Innate Immune Pattern Recognition Molecules

Murugaiah

Tsolaki

Kishore

2020

Advances in Experimental Medicine and Biology

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Collectins are collagen-containing C-type (calcium-dependent) lectins which are important pathogen pattern recognising innate immune molecules. Their primary structure is characterised by an N-terminal, triple-helical collagenous region made up of Gly-X-Y repeats, an a-helical coiled-coil trimerising neck region, and a Cterminal C-type lectin or carbohydrate recognition domain (CRD). Further oligomerisation of this primary structure can give rise to more complex and multimeric structures that can be seen under electron microscope. Collectins can be found in serum as well as in a range of tissues at the mucosal surfaces. Mannanbinding lectin can activate the complement system while other members of the collectin family are extremely versatile in recognising a diverse range of pathogens via their CRDs and bring about effector functions designed at the clearance of invading pathogens. These mechanisms include opsonisation, enhancement of phagocytosis, triggering superoxidative burst and nitric oxide production. Collectins can also potentiate the adaptive immune response via antigen presenting cells such as macrophages and dendritic cells through modulation of cytokines and chemokines, thus they can act as a link between innate and adaptive immunity. This chapter describes the structure-function relationships of collectins, their diverse functions, and their interaction with viruses, bacteria, fungi and parasites.

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“…At the first stages of T. cruzi infection (seconds after infection), complement can be initially activated by the LP and AP since both pathways do not depend on a specific antibody response (Cestari et al, 2013). Thus, trypomastigotes can immediately be targeted by complement after accessing the host bloodstream.…”

Section: The Complement Systemmentioning

confidence: 99%

“…A wide range of carbohydrates (such as GalNAc and GlcNAc) anchored by glycosylphosphatidylinositol in the outer leaflet of T. cruzi plasma membrane (Lederkremer and Bertello, 2001; Buscaglia et al, 2006) can be recognized by PAMP sensor molecules, such as MBL and ficolins (Cestari et al, 2009; Cestari and Ramirez, 2010) leading to the activation of MASPs. Then, the serine protease MASP-2 cleaves C2 and C4 generating LP C3 convertase formation that activates C3 to form C3b, contributing to the AP amplification loop with simultaneous LP and AP activation (Ricklin et al, 2010; Cestari et al, 2013). In addition, the activation of the AP can also take place spontaneously by hydrolysis of C3, which leads to the generation of C3 convertase and C3 cleavage.…”

Section: The Complement Systemmentioning

confidence: 99%

The Complement System: A Prey of Trypanosoma cruzi

et al. 2017

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Trypanosoma cruzi is a protozoan parasite known to cause Chagas disease (CD), a neglected sickness that affects around 6–8 million people worldwide. Originally, CD was mainly found in Latin America but more recently, it has been spread to countries in North America, Asia, and Europe due the international migration from endemic areas. Thus, at present CD represents an important concern of global public health. Most of individuals that are infected by T. cruzi may remain in asymptomatic form all lifelong, but up to 40% of them will develop cardiomyopathy, digestive mega syndromes, or both. The interaction between the T. cruzi infective forms and host-related immune factors represents a key point for a better understanding of the physiopathology of CD. In this context, the complement, as one of the first line of host defense against infection was shown to play an important role in recognizing T. cruzi metacyclic trypomastigotes and in controlling parasite invasion. The complement consists of at least 35 or more plasma proteins and cell surface receptors/regulators, which can be activated by three pathways: classical (CP), lectin (LP), and alternative (AP). The CP and LP are mainly initiated by immune complexes or pathogen-associated molecular patterns (PAMPs), respectively, whereas AP is spontaneously activated by hydrolysis of C3. Once activated, several relevant complement functions are generated which include opsonization and phagocytosis of particles or microorganisms and cell lysis. An important step during T. cruzi infection is when intracellular trypomastigotes are release to bloodstream where they may be target by complement. Nevertheless, the parasite uses a sequence of events in order to escape from complement-mediated lysis. In fact, several T. cruzi molecules are known to interfere in the initiation of all three pathways and in the assembly of C3 convertase, a key step in the activation of complement. Moreover, T. cruzi promotes secretion of plasma membrane-derived vesicles from host cells, which prevent the activity of C3 convertase C4b2a and thereby may hinder complement. In this review, we aim to present an overview on the strategies used by T. cruzi in order to circumvent the activation of complement and, consequently, its biological effects.

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Mechanisms of complement lectin pathway activation and resistance by trypanosomatid parasites

Cited by 40 publications

References 63 publications

Differential ability to resist to complement lysis and invade host cells mediated by MBL in R4 and 860 strains of Trypanosoma cruzi

Differential ability to resist to complement lysis and invade host cells mediated by MBL in R4 and 860 strains of Trypanosoma cruzi

Collectins: Innate Immune Pattern Recognition Molecules

The Complement System: A Prey of Trypanosoma cruzi

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