Role of GP82 in the selective binding to gastric mucin during oral infection with Trypanosoma cruzi.
Oral infection by Trypanosoma cruzi has been the primary cause of recent outbreaks of acute Chagas' diseases. This route of infection may involve selective binding of the metacyclic trypomastigote surface molecule gp82 to gastric mucin as a first step towards invasion of the gastric mucosal epithelium and subsequent systemic infection. Here we addressed that question by performing in vitro and in vivo experiments. A recombinant protein containing the complete gp82 sequence (J18), a construct lacking the gp82 central domain (J18*), and 20-mer synthetic peptides based on the gp82 central domain, were used for gastric mucin binding and HeLa cell invasion assays, or for in vivo experiments. Metacyclic trypomastigotes and J18 bound to gastric mucin whereas J18* failed to bind. Parasite or J18 binding to submaxillary mucin was negligible. HeLa cell invasion by metacyclic forms was not affected by gastric mucin but was inhibited in the presence of submaxillary mucin. Of peptides tested for inhibition of J18 binding to gastric mucin, the inhibitory peptide p7 markedly reduced parasite invasion of HeLa cells in the presence of gastric mucin. Peptide p7*, with the same composition as p7 but with a scrambled sequence, had no effect. Mice fed with peptide p7 before oral infection with metacyclic forms developed lower parasitemias than mice fed with peptide p7*. Our results indicate that selective binding of gp82 to gastric mucin may direct T. cruzi metacyclic trypomastigotes to stomach mucosal epithelium in oral infection.
Staquicini
Daniela I
DI
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brasil.
Martins
Rafael M
RM
Macedo
Silene
S
Sasso
Gisela R S
GR
Atayde
Vanessa D
VD
Juliano
Maria A
MA
Yoshida
Nobuko
N
D000818:Animals; D002448:Cell Adhesion; D014355:Chagas Disease / Q000469:parasitology; D004847:Epithelial Cells / Q000469:parasitology; D005260:Female; D005752:Gastric Mucins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*; D013552:Swine; D014349:Trypanosoma cruzi / Q000472:pathogenicity*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
D005752:Gastric Mucins; D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; D037521:Virulence Factors; C527132:glycoprotein GP82, Trypanosoma cruzi