Abstract
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.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adolescent
-
Adult
-
Aged
-
B-Lymphocytes / drug effects
-
B-Lymphocytes / immunology
-
B-Lymphocytes / metabolism*
-
Chemokines, CC / pharmacology
-
Chemotaxis / drug effects
-
Chemotaxis / immunology
-
Crohn Disease / immunology
-
Crohn Disease / pathology
-
Dental Prophylaxis
-
Female
-
Gene Expression / drug effects
-
Humans
-
Ileum / immunology
-
Ileum / metabolism
-
Ileum / pathology
-
Immunity, Mucosal / immunology*
-
Immunoglobulin A / biosynthesis*
-
Immunoglobulin J-Chains / metabolism
-
Immunoglobulin M / metabolism
-
Inflammatory Bowel Diseases / immunology
-
Interleukin-10 / pharmacology
-
Intestinal Mucosa / immunology
-
Intestinal Mucosa / metabolism
-
Intestinal Mucosa / pathology
-
Lipopolysaccharides / blood
-
Lipopolysaccharides / pharmacology
-
Male
-
Middle Aged
-
Palatine Tonsil / cytology
-
Palatine Tonsil / immunology
-
Porins / immunology
-
Porins / pharmacology
-
Receptors, CCR / genetics
-
Receptors, CCR / metabolism
-
Receptors, CCR10 / genetics
-
Receptors, CCR10 / metabolism
-
Receptors, Lymphocyte Homing / metabolism*
-
Toll-Like Receptor 2 / metabolism*
-
Young Adult
Substances
-
CC chemokine receptor 9
-
CCL25 protein, human
-
CCL28 protein, human
-
CCR10 protein, human
-
Chemokines, CC
-
Immunoglobulin A
-
Immunoglobulin J-Chains
-
Immunoglobulin M
-
Lipopolysaccharides
-
Porins
-
Receptors, CCR
-
Receptors, CCR10
-
Receptors, Lymphocyte Homing
-
Toll-Like Receptor 2
-
porin protein, Neisseria
-
Interleukin-10