Lipopolysaccharides-Induced Suppression of Innate-Like B Cell Apoptosis Is Enhanced by CpG Oligodeoxynucleotide and Requires Toll-Like Receptors 2 and 4.
Innate-like B lymphocytes play an important role in innate immunity in periodontal disease through Toll-like receptor (TLR) signaling. However, it is unknown how innate-like B cell apoptosis is affected by the periodontal infection-associated innate signals. This study is to determine the effects of two major TLR ligands, lipopolysaccharide (LPS) and CpG-oligodeoxynucleotides (CpG-ODN), on innate-like B cell apoptosis. Spleen B cells were isolated from wild type (WT), TLR2 knockout (KO) and TLR4 KO mice and cultured with E. coli LPS alone, P. gingivalis LPS alone, or combined with CpG-ODN for 2 days. B cell apoptosis and expressions of specific apoptosis-related genes were analyzed by flow cytometry and real-time PCR respectively. P. gingivalis LPS, but not E. coli LPS, reduced the percentage of AnnexinV+/7-AAD- cells within IgMhighCD23lowCD43-CD93- marginal zone (MZ) B cell sub-population and IgMhighCD23lowCD43+CD93+ innate response activator (IRA) B cell sub-population in WT but not TLR2KO or TLR4KO mice. CpG-ODN combined with P. gingivalis LPS further reduced the percentage of AnnexinV+/7-AAD- cells within MZ B cells and IRA B cells in WT but not TLR2 KO or TLR4 KO mice. Pro-apoptotic CASP4, CASP9 and Dapk1 were significantly down-regulated in P. gingivalis LPS- and CpG-ODN-treated B cells from WT but not TLR2 KO or TLR4 KO mice. Anti-apoptotic IL-10 was significantly up-regulated in P. gingivalis LPS- and CpG-ODN-treated B cells from WT and TLR2 KO but not TLR4 KO mice. These results suggested that both TLR2 and TLR4 signaling are required for P. gingivalis LPS-induced, CpG-ODN-enhanced suppression of innate-like B cell apoptosis.
The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, United States of America.|Peking University School and Hospital of Stomatology, Department of Periodontology, Beijing, China.
Xiaoqian
X
Yu
The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, United States of America.|Ninth People's Hospital, College of Stomatology, Shanghai JiaoTong University School of Medicine, Department of Prosthodontics, Shanghai Key laboratory, Shanghai, China.
Yuhua
Y
Wang
The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, United States of America.|The Fourth Hospital of Harbin Medical University, Department of stomatology, Harbin, China.
Jiang
J
Lin
The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, United States of America.
Yang
Y
Hu
The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, United States of America.
Toshihisa
T
Kawai
The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, United States of America.
Martin A
MA
Taubman
The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, MA, United States of America.
Xiaozhe
http://orcid.org/0000-0001-8357-1471
X
Han
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D007113:Immunity, Innate / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D016966:Porphyromonas gingivalis / Q000737:chemistry; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
C408982:CPG-oligonucleotide; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4