Nasal cholera toxin elicits IL-5 and IL-5 receptor alpha-chain expressing B-1a B cells for innate mucosal IgA antibody responses.
In this study, we examine whether native cholera toxin (nCT) as a mucosal adjuvant can support trinitrophenyl (TNP)-LPS-specific mucosal immune responses. C57BL/6 mice were given nasal TNP-LPS in the presence or absence of nCT. Five days later, significantly higher levels of TNP-specific mucosal IgA Ab responses were induced in the nasal washes, saliva, and plasma of mice given nCT plus TNP-LPS than in those given TNP-LPS alone. High numbers of TNP-specific IgA Ab-forming cells were also detected in mucosal tissues such as the nasal passages (NPs), the submandibular glands (SMGs), and nasopharyngeal-associated lymphoreticular tissue of mice given nCT. Flow cytometric analysis showed that higher numbers of surface IgA+, CD5+ B cells (B-1a B cells) in SMGs and NPs of mice given nasal TNP-LPS plus nCT than in those given TNP-LPS alone. Furthermore, increased levels of IL-5R alpha-chain were expressed by B-1a B cells in SMGs and NPs of mice given nasal TNP-LPS plus nCT. Thus, CD4+ T cells from these mucosal effector lymphoid tissues produce high levels of IL-5 at both protein and mRNA levels. When mice were treated with anti-IL-5 mAb, significant reductions in TNP-specific mucosal IgA Ab responses were noted in external secretions. These findings show that nasal nCT as an adjuvant enhances mucosal immune responses to a T cell-independent Ag due to the cross-talk between IL-5Ralpha+ B-1a B cells and IL-5-producing CD4+ T cells in the mucosal effector lymphoid tissues.
Kataoka
Kosuke
K
Department of Pediatric Dentistry, Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Fujihashi
Keiko
K
Sekine
Shinichi
S
Fukuiwa
Tatsuya
T
Kobayashi
Ryoki
R
Suzuki
Hideaki
H
Nagata
Hideki
H
Takatsu
Kiyoshi
K
Shizukuishi
Satoshi
S
McGhee
Jerry R
JR
Fujihashi
Kohtaro
K
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000955:Antigens, T-Independent / Q000008:administration & dosage / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000097:blood; D015848:Interleukin-5 / Q000096:biosynthesis*; D053666:Interleukin-5 Receptor alpha Subunit / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology*; D013363:Submandibular Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000955:Antigens, T-Independent; D018985:Epitopes, B-Lymphocyte; D051858:Forkhead Transcription Factors; C491332:Foxb1 protein, mouse; D007070:Immunoglobulin A; D015848:Interleukin-5; D053666:Interleukin-5 Receptor alpha Subunit; D008070:Lipopolysaccharides; C048761:trinitrophenyl-lipopolysaccharide; D002772:Cholera Toxin