Mast cells contribute to the mucosal adjuvant effect of CTA1-DD after IgG-complex formation.
Mast cell activation is one of the most dramatic immune-mediated responses the body can encounter. In the worst scenario (i.e., anaphylaxis), this response is fatal. However, the importance of mast cells as initiators and effectors of both innate and adaptive immunity in healthy individuals has recently been appreciated. It was reported that mast cell activation can be used as an adjuvant to promote Ag-specific humoral immune responses upon vaccination. In this study, we have used a clinically relevant mucosal adjuvant, cholera toxin A1 subunit (CTA1)-DD, which is a fusion protein composed of CTA1, the ADP-ribosylating part of cholera toxin, and DD, two Ig-binding domains derived from Staphylococcus aureus protein A. CTA1-DD in combination with polyclonal IgG induced degranulation and production of TNF-alpha from mouse mast cells. Furthermore, CTA1-DD and polyclonal IgG complex induced mast cell degranulation in mouse skin tissue and nasal mucosa. We also found that intranasal immunization with hapten (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to chicken gammaglobulin admixed with CTA1-DD complexed with polyclonal IgG greatly enhanced serum IgG anti-NP Ab responses and stimulated higher numbers of NP-specific plasma cells in the bone marrow as compared with that observed in mice immunized with NP-chicken gammaglobulin with CTA1-DD alone. This CTA1-DD/IgG complex-mediated enhancement was mast cell dependent because it was absent in mast cell-deficient Kit(W-sh/W-sh) mice. In conclusion, our data suggest that a clinically relevant adjuvant, CTA1-DD, exerts additional augmenting effects through activation of mucosal mast cells, clearly demonstrating that mast cells could be further exploited for improving the efficacy of mucosal vaccines.
Fang
Yu
Y
Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Larsson
Lisa
L
Mattsson
Johan
J
Lycke
Nils
N
Xiang
Zou
Z
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000502:physiology; D000818:Animals; D000936:Antigen-Antibody Complex / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000502:physiology; D018928:Immunity, Mucosal / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000502:physiology
D000276:Adjuvants, Immunologic; D000936:Antigen-Antibody Complex; C440610:CTA1-DD protein, recombinant; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D002772:Cholera Toxin; D019009:Proto-Oncogene Proteins c-kit