Abstract
The complement system is the main arm of the vertebrate innate immune system against pathogen infection. For the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, subverting the complement system and invading the host cells is crucial to succeed in infection. However, little attention has focused on whether the complement system can effectively control T. cruzi infection. To address this question, we decided to analyse: 1) which complement pathways are activated by T. cruzi using strains isolated from different hosts, 2) the capacity of these strains to resist the complement-mediated killing at nearly physiological conditions, and 3) whether the complement system could limit or control T. cruzi invasion of eukaryotic cells. The complement activating molecules C1q, C3, mannan-binding lectin and ficolins bound to all strains analysed; however, C3b and C4b deposition assays revealed that T. cruzi activates mainly the lectin and alternative complement pathways in non-immune human serum. Strikingly, we detected that metacyclic trypomastigotes of some T. cruzi strains were highly susceptible to complement-mediated killing in non-immune serum, while other strains were resistant. Furthermore, the rate of parasite invasion in eukaryotic cells was decreased by non-immune serum. Altogether, these results establish that the complement system recognizes T. cruzi metacyclic trypomastigotes, resulting in killing of susceptible strains. The complement system, therefore, acts as a physiological barrier which resistant strains have to evade for successful host infection.
Highlights
Chagas disease is an illness that affects 18 million people in Latin America [1]
The complement system can be activated by three pathways: classical, activated when IgG or IgM bind to the pathogen surface and associate with the C1 complex (C1qr2s2), which cleaves C2 and C4 to form C3 convertase (C4b2a); lectin, activated when mannan-binding lectins (MBLs), L-ficolins or Hficolins bind to the pathogen surface and associate with MBLassociated serine protease-2 (MASP2) to cleave C2 and C4, generating C3 convertase; and alternative, activated when C3b binds to the pathogen surface and associates with factor B to form C3 convertase (C3bBb) [9]
The host innate immune system is the major barrier for pathogens to succeed in infection, and the complement system is one of the main arms of host defense [9]
Summary
Chagas disease is an illness that affects 18 million people in Latin America [1]. It is caused by the protozoan parasite Trypanosoma cruzi and is mainly transmitted by triatomine insects, congenital, oral and blood transfusion transmission has been reported [2,3,4,5,6,7]. Bloodstream trypomastigotes sensitized with antibodies from acutely infected animals were killed by the complement system in human serum [20,21], and anti-agalactosyl antibodies recognizing O-linked oligosaccharides on T. cruzi mucin-like GPI-anchored proteins were identified in chronic phase Chagas disease patients [22,23]. These data support the idea that the complement system can recognize and kill the infectious stages of T. cruzi. The rate of T. cruzi invasion of eukaryotic cells was significantly reduced in the presence of non-immune human serum, showing that the complement system acts as a physiological barrier for T. cruzi infection and strains resistant to complement system have a higher chance to succeed in the infection
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