3',5'-Cyclic diguanylic acid elicits mucosal immunity against bacterial infection.
3',5'-Cyclic diguanylic acid (cdiGMP) is emerging as a universal bacterial second messenger in regulating bacterial growth on surfaces. It has been recently shown that cdiGMP stimulates innate immunity and enhances antigen-specific humoral and cellular immune responses. We herein report that intranasal (i.n.) administration with cdiGMP induces an acute but transient inflammatory response and activation of dendritic cells in the lungs. Moreover, i.n. immunization of mice with pneumococcal surface adhesion A (PsaA) in conjunction with cdiGMP elicited strong antigen-specific serum immunoglobulin G (IgG) and secretory IgA antibody responses at multiple mucosal surfaces. More importantly, the immunized mice showed significantly reduced nasopharyngeal Streptococcus pneumoniae colonization. These results, for the first time, provide direct evidence for the induction of protection against mucosal bacterial infections by cdiGMP as an adjuvant.
Yan
Hongbin
H
Department of Chemistry, Brock University, St. Catharines, Ontario, Canada. tyan@brocku.ca
KuoLee
Rhonda
R
Tram
Kha
K
Qiu
Hongyu
H
Zhang
Jianbing
J
Patel
Girishchandra B
GB
Chen
Wangxue
W
D000281:Administration, Intranasal; D000818:Animals; D006152:Cyclic GMP / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D018928:Immunity, Mucosal / Q000187:drug effects; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP