The house dust mite allergen, Dermatophagoides pteronyssinus, promotes type 2 responses by modulating the balance between IL-4 and IFN-gamma.
A common property of allergens is their potential to generate type 2 cytokine responses. To understand the mechanisms involved in this phenomenon, we have evaluated the polarizing potential of a major allergen, Dermatophagoides pteronyssinus 1 (Der p 1), in an heterologous immunization system using the glutathione S-transferase of the parasite Schistosoma mansoni (Sm28-GST) as immunogen. In previous studies, we showed that immunization with the Sm28-GST emulsified in CFA induced a nonpolarized immune response. In contrast, when alum was used as adjuvant, a type 2 immune response was induced against Sm28-GST. Using this experimental model, we examined whether the administration of Der p 1 together with Sm28-GST influenced the nonpolarized and/or the Th2 profiles induced by the CFA or the alum immunization, respectively. Our results showed that the introduction of Der p 1 in the CFA immunization protocol was associated with diminished anti-Sm28-GST IgG2a Ab titers, reduced IFN-gamma mRNA expression, and frequency of IFN-gamma-producing cells. In contrast, the introduction of Der p 1 in the alum protocol did not affect IL-4 or Ig isotype responses. The effect of Der p 1 was specific, since coimmunization with tetanus toxin fragment C did not affect the profile of the response against Sm28-GST. Furthermore, inactivation of Der p 1 reduced its ability to modify the immune response profile, suggesting that its protease activity played an important role in deviating the immune response. Our results suggest that the Der p 1 has the ability to modify the profile of an immune response by modulating the balance between the polarizing cytokines IL-4 and IFN-gamma.
Comoy
E E
EE
INSERM U167 Institut Pasteur de Lille, France.
Pestel
J
J
Duez
C
C
Stewart
G A
GA
Vendeville
C
C
Fournier
C
C
Finkelman
F
F
Capron
A
A
Thyphronitis
G
G
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology*; D000485:Allergens / Q000008:administration & dosage / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides; D003546:Cysteine Endopeptidases / Q000276:immunology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005260:Female; D005982:Glutathione Transferase / Q000008:administration & dosage / Q000276:immunology; D006023:Glycoproteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology*; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008925:Mites / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000485:Allergens; D039741:Antigens, Dermatophagoides; D015853:Cysteine Proteinase Inhibitors; D006023:Glycoproteins; D007132:Immunoglobulin Isotypes; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D005982:Glutathione Transferase; D003546:Cysteine Endopeptidases