A surface membrane protein of Entamoeba histolytica functions as a receptor for human chemokine IL-8: its role in the attraction of trophozoites to inflammation sites.
Entamoeba histolytica trophozoites respond to the presence of IL-8, moving by chemotaxis towards the source of the chemokine. IL-8 binds to the trophozoite membrane and triggers a response that activates signaling pathways that in turn regulate actin/myosin cytoskeleton organisation to initiate migration towards the chemokine, suggesting the presence of a receptor for IL-8 in the parasite. Antibodies directed to the human IL-8 receptor (CXCR1) specifically recognised a 29 kDa protein in trophozoite membrane fractions. The same protein was immunoprecipitated by this antibody from total amebic extracts. Peptide analysis of the immunoprecipitated protein revealed a sequence with high homology to a previously identified amebic outer membrane peroxiredoxin and a motif within the third loop of human CXCR1, which is an important site for IL-8 binding and activation of signaling processes. Immunodetection assays demonstrated that the anti-human CXCR1 antibody binds to the 29 kDa protein in a different but close site to where IL-8 binds to the trophozoite surface membrane, suggesting that human and amebic receptors for this chemokine share common epitopes. In the context of the human intestinal environment, a receptor for IL-8 could be a great advantage for E. histolytica trophozoite survival, as they could reach an inflammatory milieu containing abundant nutrients. In addition, it has been suggested that the high content of accessible thiol groups of the protein and its peroxidase activity could provide protection in the oxygen rich milieu of colonic lesions, allowing trophozoite invasion of other tissues and escape from the host immune response.
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México, DF 07630, Mexico.
J Daniel
JD
Diaz-Valencia
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México, DF 07630, Mexico.
Eloy Andrés
EA
Pérez-Yépez
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico.
Jorge Tonatiuh
JT
Ayala-Sumuano
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México, DF 07630, Mexico.
Elizabeth
E
Franco
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México, DF 07630, Mexico. Electronic address: imeza@cinvestav.mx.
Isaura
I
Meza
D002465:Cell Movement; D002633:Chemotaxis; D004748:Entamoeba histolytica / Q000187:drug effects / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation / Q000469:parasitology / Q000473:pathology; D016209:Interleukin-8 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D053700:Receptors, Interleukin-8 / Q000378:metabolism*; D053058:Trophozoites / Q000502:physiology
D016209:Interleukin-8; D008565:Membrane Proteins; D053700:Receptors, Interleukin-8
Chemotaxis; Entamoeba histolytica; IL-8 receptor; Peroxiredoxin; Tissue invasion