Fasciola hepatica cathepsin L cysteine proteinase suppresses Bordetella pertussis-specific interferon-gamma production in vivo.
We have previously demonstrated that Fasciola hepatica infection significantly reduced Bordetella pertussis-specific interferon (IFN)-gamma production in mice coinfected with B. pertussis or immunized with a pertussis whole cell vaccine (Pw). In the present study, we have identified parasite molecules capable of mimicking this suppressive effect of F. hepatica. Parenteral injection of mice with culture medium in which adult F. hepatica were maintained (excretory/secretory, ES, products) suppressed B. pertussis-specific IFN-gamma production in mice immunized with Pw. The suppressive effect of ES was abrogated by coinjecting ES with the cysteine proteinase inhibitor, Z-Phe-Ala-diazomethylketone. Furthermore, purified cathepsin L proteinase (FheCL), a major component of ES products, was capable of suppressing IFN-gamma production. The suppressive effect of FheCL was attenuated in interleukin (IL)-4 defective (IL-4-/-) mice. Therefore, FheCL released by F. hepatica is involved in the suppression of Th1 immune responses and this suppression may be dependent upon IL-4.
O'Neill
S M
SM
Molecular Parasitology, School of Biotechnology, Faculty of Health and Science, Dublin City University, Glasnevin, Dublin, Ireland.
Mills
K H
KH
Dalton
J P
JP
D000818:Animals; D001428:Bacterial Vaccines; D001886:Bordetella pertussis / Q000187:drug effects / Q000276:immunology*; D056668:Cathepsin L; D002403:Cathepsins / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000494:pharmacology; D003978:Diazomethane / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005210:Fasciola hepatica / Q000201:enzymology*; D005260:Female; D007114:Immunization; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology; D007659:Ketones / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout
D001428:Bacterial Vaccines; D004791:Enzyme Inhibitors; D007659:Ketones; C016047:N-benzyloxycarbonylphenylalanine diazomethyl ketone; D015847:Interleukin-4; D003978:Diazomethane; D007371:Interferon-gamma; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse