Nasopharyngeal-associated lymphoreticular tissue (NALT) immunity: fimbriae-specific Th1 and Th2 cell-regulated IgA responses for the inhibition of bacterial attachment to epithelial cells and subsequent inflammatory cytokine production.
To investigate the antibacterial activity of mucosal Th1 and Th2 immune responses induced nasally and orally, mice were immunized with mucosal vaccine containing fimbrial protein of Porphyromonas gingivalis, a causative agent for a destructive chronic inflammation in the periodontium, and cholera toxin (CT) as mucosal adjuvant. Nasal vaccine containing low doses of fimbriae (10 micrograms) and CT (1 microgram) induced Ag-specific Th1/Th2-type response in CD4+ T cells in mucosal effector tissues, including nasal passage and submandibular glands, which accounted for the generation of Ag-specific IgA-producing cells. In contrast, oral immunization required higher amounts of fimbriae and CT for the induction of Ag-specific IgA responses. Fimbriae-specific IgA mAbs generated from submandibular glands of nasally immunized mice inhibited P. gingivalis attachment to and reduced subsequent inflammatory cytokine production from epithelial cells. These findings suggest that nasal vaccination is an effective immunization regimen for the induction of Ag-specific Th1 and Th2 cell-driven IgA immune responses that possess the ability to inhibit bacterial attachment to epithelial cells and subsequent inflammatory cytokine production.
Yanagita
M
M
Department of Mucosal Immunology, Faculty of Dentistry, Osaka University, Japan.
Hiroi
T
T
Kitagaki
N
N
Hamada
S
S
Ito
H O
HO
Shimauchi
H
H
Murakami
S
S
Okada
H
H
Kiyono
H
H
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001422:Bacterial Adhesion / Q000276:immunology*; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D005260:Female; D010861:Fimbriae, Bacterial / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D007624:KB Cells; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012157:Mononuclear Phagocyte System / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D009061:Mouth Mucosa / Q000276:immunology; D009297:Nasal Mucosa / Q000276:immunology; D009305:Nasopharynx / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D013363:Submandibular Gland / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology* / Q000382:microbiology
D016207:Cytokines; D007070:Immunoglobulin A; D002772:Cholera Toxin