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

Abstract

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.

Is It Possible to Intervene in the Capacity of Trypanosoma cruzi to Elicit and Evade the Complement System?

“…TcCRP promotes evasion of immune response, in a TS-independent manner ( 69 – 71 ). As expected, positive correlations between the virulence of T. cruzi strains and TcCRP expression levels ( 72 ) or mRNA levels ( 41 ) have been described. Moreover, TcCRP is immunogenic and induces lytic antibodies in humans and mice ( 32 ) and a DNA-based immunization confers protection against T. cruzi infection in mice ( 33 ).…”

“…CRIT is expressed in different T. cruzi strains and clones, such as CL Brenner, Colombiana and Dm28c, with high sequence identity (88 - 98%) ( 23 ), but apparently its gene is only functional in some T. cruzi lineages. A recent study evaluating the resistance of C in different TcI strains with high (Qro) and low (Ninoa) virulence, demonstrated that the mRNA of CRIT is three – fold lower in the low virulence strain ( 41 ).…”

“…T-DAF is functionally, but not structurally analogous to human DAF ( 21 ). T-DAF mRNA levels are lower in C-susceptible T. cruzi strains ( 41 ). A partial T-DAF cDNA clone and its deduced protein sequence showed 40% homology with a portion of the coding region for DAF ( 21 ).…”

Trypanosoma cruzi pathogenicity involves virulence factor expression and upregulation of bioenergetic and biosynthetic pathways

“…TS also participates in host immune evasion [ 116–119 ], and CRPs, which are present only on trypomastigotes, block complement system activation [ 120 ]. In addition, the complement system modulates the infectivity of susceptible T. cruzi TcI strains [ 121 ]. Thus, CRP expression appears to be closely related to T. cruzi virulence [ 10 ], which was supported in the current study.…”

Ficolin‐3 in chronic Chagas disease: Low serum levels associated with the risk of cardiac insufficiency

“…[13][14][15] The complement system was shown to play an important role in controlling T cruzi invasion of eukaryotic cells and killing of metacyclic trypomastigotes in non-immune serum, 16,17 thereby having a potential influence in the successful establishment of both host infection and CD clinical forms. 15,18 All three complement pathways were shown to be triggered by T cruzi infection using in vitro assays, 16,19,20 with LP and AP becoming activated in non-immune human serum. 16 The LP is initiated by binding of the host pattern recognition molecules (PRMs) mannose-binding lectin (MBL), collectin-10 (CL-10 or CL-L1) and collectin-11 (CL-11 or CL-K1), ficolin-1, ficolin-2 or ficolin-3 to pathogen-associated molecular patterns (PAMPs) on the parasite surface.…”