Exogenous Calreticulin, incorporated onto non-infective Trypanosoma cruzi epimastigotes, promotes their internalization into mammal host cells

Sosoniuk-Roche, Eduardo; Vallejos, Gerardo; Pizarro-Bäuerle, Javier; Weinberger, Katherine; Rosas, Carlos; Valck, Carolina; Michalak, Marek; Ferreira, Arturo

doi:10.1016/j.imbio.2016.10.020

Cited by 10 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have proposed that the TcCalr/C1q complex is recognized as an "eat me" signal on the parasite by host Calr on phagocytes and other cellular types, thus promoting infectivity (Figure 1). In agreement with these findings, Calr-deficient fibroblasts are unable to internalize these parasites (52). Moreover, in mice inoculated with trypomastigotes, carrying a monoallelic TcCalr deletion, no parasitemia, nor anti-T. cruzi IgG levels are detected, demonstrating that these mutants have a potent restriction in their capacity to infect host cells, due to insufficient Calr expression and consequent reduced resistance to C (49).…”

Section: Tccalr/c1 Interaction: Role In Promoting Infectivitysupporting

confidence: 70%

“…Non-infective epimastigotes express less TcCalr on their surface ( 36 , 51 ), which may contribute to their high sensitivity to C and lack of infectivity. In agreement with this notion, when exogenous TcCalr is added, epimastigotes are internalized by fibroblasts, in a C1q-dependent manner ( 52 ).…”

Section: Tccalr/c1 Interaction: Role In Promoting Infectivitymentioning

confidence: 69%

See 1 more Smart Citation

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Tccalr/c1 Interaction: Role In Promoting Infectivitysupporting

confidence: 70%

Section: Tccalr/c1 Interaction: Role In Promoting Infectivitymentioning

confidence: 69%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…TcCRT has been reported as an efficient complement-inhibitory protein and a potent virulence properties favouring the invasion of T. cruzi by coating the parasite with inactive C1q, which can still work as an apoptotic signal to trigger phagocytosis by macrophages. It also favours the attachment and invasion of host-cell membrane by binding to host calreticulin, as has been seen in the colonisation of placental tissue ( Castillo et al 2013 ), and more recently, using TcCRT-coated epimastigotes invading mammalian cells ( Sosoniuk-Roche et al 2017 ). We propose that in the GPS plus Man+NAcGlc condition, not only are Ninoa TCT free of the lytic activity of the lectin pathway, which is a major contributor of complement activation and complement-mediated killing ( Fig.…”

Section: Discussionmentioning

confidence: 98%

Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi

Arroyo-Olarte

Martı́nez

Cruz-Rivera

et al. 2018

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

BACKGROUND Trypanosoma cruzi is a protozoan parasite and an etiological agent of Chagas disease. There is a wide variability in the clinical outcome of its infection, ranging from asymptomatic individuals to those with chronic fatal mega syndromes. Both parasite and host factors, as well as their interplay, are thought to be involved in the process.OBJECTIVES To evaluate the resistance to complement-mediated killing in two T. cruzi TcI strains with differential virulence and the subsequent effect on their infectivity in mammalian cells.METHODS Tissue-culture derived trypomastigotes of both strains were incubated in guinea pig serum and subjected to flow cytometry in order to determine their viability and complement activations. Trypomastigotes were also incubated on host cells monolayers in the presence of serum, and infectivity was evaluated under different conditions of complement pathway inhibition. Relative expression of the main parasite-specific complement receptors between the two strains was assessed by quantitative real-time polymerase chain reaction.FINDINGS In this work, we showed that two TcI strains, one with lower virulence (Ninoa) compared to the other (Qro), differ in their resistance to the lytic activity of complement system, hence causing a compromised ability of Ninoa strain to invade mammalian cells. These results correlate with the three-fold lower messenger RNA (mRNA) levels of complement regulatory protein (CRP), trypomastigote-decay acceleration factor (T-DAF), and complement C2 receptor inhibitor trispanning (CRIT) in Ninoa compared to those in Qro. On the other hand, calreticulin (CRT) mRNA and surface protein levels were higher in Ninoa strain and promoted its infectivity when the lectin pathway of the complement system was inhibited.MAIN CONCLUSIONS This work suggests the complex interplay of CRP, T-DAF, CRIT, and CRT, and the diagnostic value of mRNA levels in the assessment of virulence potential of T. cruzi strains, particularly when dealing with isolates with similar genetic background.

show abstract

“…Similarly, CRT of T. cruzi could bind to the collagenous portion of L-ficolin to inhibit the activation of the lectin pathway (Sosoniuk et al, 2014). Tc-CRT also bound MBL thus inactivating the lectin pathway (Lidani et al, 2017; Sosoniuk-Roche et al, 2017). Two scabies mite proteins, SMIPP-S D1 and I1, were also shown to be capable of binding with MBL to inhibit activation of the MBL-initiated lectin pathway (Reynolds et al, 2014).…”

Section: Complement Evasion By Parasitesmentioning

confidence: 99%

Complement Evasion: An Effective Strategy That Parasites Utilize to Survive in the Host

et al. 2019

View full text Add to dashboard Cite

Parasitic infections induce host immune responses that eliminate the invading parasites. However, parasites have evolved to develop many strategies to evade host immune attacks and survive in a hostile environment. The complement system acts as the first line of immune defense to eliminate the invading parasites by forming the membrane attack complex (MAC) and promoting an inflammatory reaction on the surface of invading parasites. To date, the complement activation pathway has been precisely delineated; however, the manner in which parasites escape complement attack, as a survival strategy in the host, is not well understood. Increasing evidence has shown that parasites develop sophisticated strategies to escape complement-mediated killing, including (i) recruitment of host complement regulatory proteins on the surface of the parasites to inhibit complement activation; (ii) expression of orthologs of host RCA to inhibit complement activation; and (iii) expression of parasite-encoded proteins, specifically targeting different complement components, to inhibit complement function and formation of the MAC. In this review, we compiled information regarding parasitic abilities to escape host complement attack as a survival strategy in the hostile environment of the host and the mechanisms underlying complement evasion. Effective escape of host complement attack is a crucial step for the survival of parasites within the host. Therefore, those proteins expressed by parasites and involved in the regulation of the complement system have become important targets for the development of drugs and vaccines against parasitic infections.

show abstract

Exogenous Calreticulin, incorporated onto non-infective Trypanosoma cruzi epimastigotes, promotes their internalization into mammal host cells

Cited by 10 publications

References 30 publications

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

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

Complement system contributes to modulate the infectivity of susceptible TcI strains of Trypanosoma cruzi

Complement Evasion: An Effective Strategy That Parasites Utilize to Survive in the Host

Contact Info

Product

Resources

About