Low potency of Chlamydophila LPS to activate human mononuclear cells due to its reduced affinities for CD14 and LPS-binding protein.
Chlamydiaceae are small obligate intracellular parasites and classified as Gram-negative bacteria. Among Chlamydiaceae-derived components, LPS is known as an immunomodulator and possesses a unique lipid A structure with longer but fewer acyl chains. In this study, to elucidate the Chlamydiaceae-induced immune responses, we evaluated the actions of Chlamydophila psittaci LPS as a Chlamydiaceae LPS on human PBMCs and compared with those of Escherichia coli LPS. Similar to E. coli LPS, C. psittaci LPS bound to monocytes and induced the pro-inflammatory cytokine production in an LPS-binding protein (LBP)-dependent manner. However, C. psittaci LPS was much less potent than E. coli LPS in both the LPS binding and cytokine production. Interestingly, although the binding of C. psittaci LPS was mediated by CD14, Toll-like receptor 4 (TLR4) and CD11b, CD14 and TLR4 but not CD11b were involved in the cytokine production. Of note, ELISA-based binding assays revealed that C. psittaci LPS directly bound to LBP and CD14; however, the affinities were much less than those of E. coli LPS. Together, these observations possibly suggest that Chlamydiaceae LPS has low binding affinities for LPS recognition molecules such as CD14 and LBP and exhibit weak biological activities against host immune cells including monocytes, thereby contributing to the chronic (persistent) inflammatory reactions during infection.
Tsutsumi-Ishii
Yuko
Y
Department of Host Defense and Biochemical Research, Juntendo University School of Medicine, Tokyo, Japan.
Shimada
Kazunori
K
Daida
Hiroyuki
H
Toman
Rudolf
R
Nagaoka
Isao
I
D000209:Acute-Phase Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002693:Chlamydiaceae / Q000276:immunology*; D002691:Chlamydophila psittaci / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D051197:Toll-Like Receptor 4; D000099231:Lipopolysaccharide-Binding Protein; C495345:TLR4 protein, human