Toll-like receptor 2 induces mucosal homing receptor expression and IgA production by human B cells.
There is a need for developing vaccines that elicit mucosal immunity. Although oral or nasal vaccination methods would be ideal, current strategies have yielded mixed success. Toll-like receptor 2 (TLR2) ligands are effective adjuvants and are currently used in the Haemophilus influenzae type B vaccine. Induction of humoral immunity in the mucosa is critical for effective vaccination; thus, we sought to determine the effects of TLR2 ligands on human mucosal B cell differentiation. We demonstrate that TLR2 ligands induce CCR9 and CCR10 expression by circulating B cells and increased chemotaxis to cognate chemokines CCL25 and CCL28 suggesting that TLR2 induces B cell homing to the gastrointestinal tract. TLR2 stimulation of B cells also induced J chain and IgA production demonstrating the induction of mucosal-like antibody secreting cells. These observations suggest that vaccines containing TLR2-ligands as adjuvants could induce mucosal B cell immunity even when delivered in a non-mucosal manner.
Section of Infectious Disease, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, MA 02118, USA.
YanMei
Y
Liang
Hatice
H
Hasturk
Jennifer
J
Elliot
Ansu
A
Noronha
Xiuping
X
Liu
Lee M
LM
Wetzler
Paola
P
Massari
Alpdogan
A
Kantarci
Harland S
HS
Winter
Francis A
FA
Farraye
Lisa M
LM
Ganley-Leal
D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D019742:Chemokines, CC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology; D003777:Dental Prophylaxis; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007144:Immunoglobulin J-Chains / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D018272:Porins / Q000276:immunology / Q000494:pharmacology; D054388:Receptors, CCR / Q000235:genetics / Q000378:metabolism; D054447:Receptors, CCR10 / Q000235:genetics / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D055815:Young Adult
C119309:CC chemokine receptor 9; C108074:CCL25 protein, human; C414047:CCL28 protein, human; C515706:CCR10 protein, human; D019742:Chemokines, CC; D007070:Immunoglobulin A; D007144:Immunoglobulin J-Chains; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D018272:Porins; D054388:Receptors, CCR; D054447:Receptors, CCR10; D016201:Receptors, Lymphocyte Homing; D051195:Toll-Like Receptor 2; C057699:porin protein, Neisseria; D016753:Interleukin-10