Trypanosoma cruzi Invasion into Host Cells: A Complex Molecular Targets Interplay.
Chagas' disease is still a worldwide threat, with estimated from 6 to 7 million infected people, mainly in Latin America. Despite all efforts, especially from international consortia (DNDi, NMTrypI), to develop an innovative therapeutic strategy against this disease, no candidate has achieved full requirements for clinical use yet. In this review, we point out the general molecular and cellular mechanisms involved in T. cruzi cell invasion and elucidate the roles of specific parasite and host targets in the progress of Chagas' disease. Among these molecular targets are Gp85/transsialidase, mucins, cruzipain and oligopeptidase B, found in parasite cell surface, and Galectin-3 and Toll-like receptors present in host cells. Thus, the deep understanding of their interplay and involvement on T. cruzi host cell adhesion, invasion and evasion from host immune may expand the chances for discovering new therapeutic agents against this neglected disease. Additionally, these targets may represent a remarkable strategy to block parasite invasion in the early stages of infection.
Vanessa Leiria
VL
Campo
Maristela Braga
MB
Martins-Teixeira
School of Pharmaceutical Sciences of Ribeirão Preto - University of São Paulo, Avenida do Café s/n, CEP 14040-903, Ribeirão Preto, SP, Brazil. carronal@usp.br.
Ivone
I
Carvalho
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D055808:Drug Discovery; D037502:Galectin 3 / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D009077:Mucins / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D015800:Protozoan Proteins; D051193:Toll-Like Receptors / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000502:physiology*
D037502:Galectin 3; D006023:Glycoproteins; D009077:Mucins; D015800:Protozoan Proteins; D051193:Toll-Like Receptors; D014344:Trypanocidal Agents; C069715:trans-sialidase; D009439:Neuraminidase; D003546:Cysteine Endopeptidases; C063214:cruzipain