Open AccessLipopolysaccharides-Induced Suppression of Innate-Like B Cell Apoptosis Is Enhanced by CpG Oligodeoxynucleotide and Requires Toll-Like Receptors 2 and 4
Author(s) -
Xiaoqian Yu,
Yuhua Wang,
Jiang Lin,
Yang Hu,
Toshihisa Kawai,
Martin A. Taubman,
Xiaozhe Han
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0165862
Subject(s) - tlr2 , innate immune system , tlr4 , cpg oligodeoxynucleotide , apoptosis , toll like receptor , population , biology , microbiology and biotechnology , tlr9 , lipopolysaccharide , immunology , inflammation , immune system , medicine , biochemistry , gene expression , dna methylation , environmental health , gene
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 IgM high CD23 low CD43 - CD93 - marginal zone (MZ) B cell sub-population and IgM high CD23 low CD43 + 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.