Trypanosoma cruzi calreticulin: A novel virulence factor that binds complement C1 on the parasite surface and promotes infectivity
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Ramírez Toloza, Galia
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Trypanosoma cruzi calreticulin: A novel virulence factor that binds complement C1 on the parasite surface and promotes infectivity
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Abstract
In Trypanosoma cruzi, calreticulin (TcCRT) translocates from the endoplasmic reticulum (ER) to the area
of flagellum emergence. We propose herein that the parasite uses this molecule to capture complement
C1, in an infective apoptotic mimicry strategy. Thus, TcCRT/C1 interactions, besides inhibiting
the classical pathway of complement activation as previously shown in our laboratories, will also
promote infectivity. This fact correlates with significant increases in TcCRT mRNA levels during early
infection stages of a VERO cell line. In vitro, the collagenous and globular C1q domains simultaneously
bind TcCRT and antigen aggregated Igs, respectively. Accordingly, mouse immunizations with TcCRT
induced humoral responses that, after challenge, correlated with increased parasitemia. Thus, on the
parasite surface, whole Igs anti-TcCRT promote C1 deposits on trypomastigotes while, as expected,
F(ab )2 fragments decrease it. Likewise, pretreatment of the parasites with whole anti-TcCRT antibodies
augmented parasitemia and mortality in mice. In contrast, pretreatment with F(ab )2 fragments
anti-TcCRT, devoid of their capacity to provide additional C1q binding sites, was protective. Most important,
while pretreatment of trypomastigotes with C1q increased infectivity in the RAW murine cell
line, as well as mice mortality and parasitemia, the F(ab )2 fragments significantly interfered with
the C1q-dependent infectivity. Differently from other surface molecules involved in infectivity, TcCRT
uses C1 as an adaptor molecule to recognize host cells. As expected, since TcCRT is one of several
cell surface parasite molecules participating in infectivity, attempts to interfere with the C1/TcCRT
interactions with F(ab )2 fragments, were moderately but significantly effective, both in vitro and
in vivo.
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Artículo de publicación ISI
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This work was supported by a grant from CONICYT-Chile (Regular
FONDECYT 1095095) and Bicentennial Collaborative Research
Projects-Chile, ACT29 and ACT112.
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URI: https://repositorio.uchile.cl/handle/2250/128922
DOI: doi:10.1016/j.imbio.2010.04.001
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Immunobiology 216 (2011) 265–273
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