Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice.
Production of neutralizing anti-IL-9 antibodies was induced in mice by immunization with mouse IL-9 coupled to ovalbumin. In the six mouse strains tested, a strong and long-lasting anti-IL-9 response developed with seric inhibitory titers of 10(-3) to 10(-5), as measured in an in vitro IL-9-dependent cell proliferation assay. In vivo, this immunization completely abrogated the increase in mast-cell protease-1 levels as well as the eosinophilia observed in mice after implantation of an IL-9-secreting tumor. We took advantage of this method to assess the role of IL-9 in infections with nematode Trichuris muris, where IL-9 production correlates with the resistant phenotype. C57BL/6 mice, which normally expel the parasite, became susceptible after anti-IL-9 immunization, demonstrating that IL-9 plays a critical role in this model. In addition, neutralization of IL-9 also inhibited parasite-induced blood eosinophilia. Taken together, the present data demonstrate the potency of our strategy to antagonize IL-9 in vivo and shows that this cytokine plays a major role in resistance against T. muris infection.
Richard
M
M
Ludwig Institute for Cancer Research, Brussels Branch, B-1200-Brussels, Belgium. richard@licr.ucl.ac.be
Grencis
R K
RK
Humphreys
N E
NE
Renauld
J C
JC
Van Snick
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002460:Cell Line; D053818:Chymases; D004802:Eosinophilia / Q000097:blood / Q000517:prevention & control*; D005260:Female; D016906:Interleukin-9 / Q000276:immunology* / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D012697:Serine Endopeptidases / Q000097:blood; D013045:Species Specificity; D014257:Trichuriasis / Q000276:immunology* / Q000469:parasitology; D014258:Trichuris / Q000276:immunology*; D014611:Vaccination
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D016906:Interleukin-9; D012697:Serine Endopeptidases; D053818:Chymases; C509230:Mcpt1 protein, mouse