Trypanosoma cruzi calreticulin inhibits the complement lectin pathway activation by direct interaction with L-Ficolin.
Trypanosoma cruzi, the agent of Chagas' disease, the sixth neglected tropical disease worldwide, infects 10-12 million people in Latin America. Differently from T. cruzi epimastigotes, trypomastigotes are complement-resistant and infective. CRPs, T-DAF, sialic acid and lipases explain at least part of this resistance. In vitro, T. cruzi calreticulin (TcCRT), a chaperone molecule that translocates from the ER to the parasite surface: (a) Inhibits the human classical complement activation, by interacting with C1, (b) As a consequence, an increase in infectivity is evident and, (c) It inhibits angiogenesis and tumor growth. We report here that TcCRT also binds to the L-Ficolin collagenous portion, thus inhibiting approximately between 35 and 64% of the human complement lectin pathway activation, initiated by L-Ficolin, a property not shared by H-Ficolin. While L-Ficolin binds to 60% of trypomastigotes and to 24% of epimastigotes, 50% of the former and 4% of the latter display TcCRT on their surfaces. Altogether, these data indicate that TcCRT is a parasite inhibitory receptor for Ficolins. The resulting evasive activities, together with the TcCRT capacity to inhibit C1, with a concomitant increase in infectivity, may represent T. cruzi strategies to inhibit important arms of the innate immune response.
Programa de Inmunología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Eduardo
E
Sosoniuk
Programa de Inmunología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Gerardo
G
Vallejos
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK; Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Hany
H
Kenawy
CNRS, Institut de Biologie Structurale JP Ebel, Grenoble, France; Université Joseph Fourier, Institut de Biologie Structurale JP Ebel, Grenoble, France.
Christine
C
Gaboriaud
CNRS, Institut de Biologie Structurale JP Ebel, Grenoble, France; Université Joseph Fourier, Institut de Biologie Structurale JP Ebel, Grenoble, France.
Nicole
N
Thielens
Department of Immunology, Fukushima Medical University, Fukushima, Japan.
Teizo
T
Fujita
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Wilhelm
W
Schwaeble
Programa de Inmunología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile. Electronic address: aferreir@med.uchile.cl.
Arturo
A
Ferreira
Programa de Inmunología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile. Electronic address: cevalck@u.uchile.cl.
Carolina
C
Valck
D001665:Binding Sites / Q000276:immunology; D037282:Calreticulin / Q000276:immunology / Q000378:metabolism*; D014355:Chagas Disease / Q000276:immunology; D003167:Complement Activation / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology*; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D037102:Lectins / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*; D000097604:Ficolins
D037282:Calreticulin; D015922:Complement C1q; D037102:Lectins; D000097604:Ficolins
Complement; Ficolins; Lectin pathway; Trypanosoma cruzi calreticulin