Airway IgG counteracts specific and bystander allergen-triggered pulmonary inflammation by a mechanism dependent on Fc gamma R and IFN-gamma.
Besides IgE, the Ab isotype that gives rise to sensitization and allergic asthma, the immune response to common inhalant allergens also includes IgG. Increased serum titers of allergen-specific IgG, induced spontaneously or by allergen vaccination, have been implicated in protection against asthma. To verify the interference of topical IgG with the allergen-triggered eosinophilic airway inflammation that underlies asthma, sensitized mice were treated by intranasal instillation of specific IgG, followed by allergen challenge. This treatment strongly reduced eosinophilic inflammation and goblet cell metaplasia, and increased Th1 reactivity and IFN-gamma levels in bronchoalveolar lavage fluid. In contrast, inflammatory responses were unaffected in IFN-gamma-deficient mice or when applying F(ab')(2). Although dependent on specific allergen-IgG interaction, inflammation triggered by bystander allergens was similarly repressed. Perseverance of inflammation repression, apparent after secondary allergen challenge, and increased allergen capture by alveolar macrophages further characterized the consequences of topical IgG application. These results assign a novel protective function to anti-allergen IgG namely at the local level interference with the inflammatory cascade, resulting in repression of allergic inflammation through an FcgammaR- and IFN-gamma-dependent mechanism. Furthermore, these results provide a basis for topical immunotherapy of asthma by direct delivery of anti-allergen IgG to the airways.
Sehra
Sarita
S
Department for Molecular Biomedical Research, Unit of Molecular Immunology, Flanders Interuniversity Institute for Biotechnology and Ghent University, Ghent, Belgium.
Pynaert
Gwenda
G
Tournoy
Kurt
K
Haegeman
Anuschka
A
Matthys
Patrick
P
Tagawa
Yohichi
Y
Pauwels
Romain
R
Grooten
Johan
J
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D024201:Bystander Effect / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000502:physiology; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000737:chemistry / Q000502:physiology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D000939:Epitopes; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D017452:Receptors, IgG; D007371:Interferon-gamma; D010047:Ovalbumin