Abstract
BACKGROUND: Human monocytic ehrlichiosis is one of the most prevalent tick-borne zoonoses caused by infection with Ehrlichia chaffeensis. Although E. chaffeensis lacks entire lipopolysaccharide and most peptidoglycan biosynthesis genes, it induces inflammatory cytokines and chemokines. Ehrlichia chaffeensis components that induce inflammation and the responsive host cell pathway are not known. METHODS: Expression of penicillin-binding protein (PBP) in E. chaffeensis was analyzed by reverse-transcription polymerase chain reaction and Bocillin FL binding assay. Next, recombinant PBP, which was high-pressure liquid chromatography purified, and native PBP of E. chaffeensis were investigated for their ability to induce proinflammatory cytokines in the human monocytic leukemia cell line THP-1 and bone marrow-derived macrophages (BMDMs) from wild-type and MyD88 knockout mice. RESULTS: Expression of PBP by E. chaffeensis was upregulated during its intracellular life cycle. PBP induced interleukin 8 or CXCL2, tumor necrosis factor α, interleukin 1β, and interleukin 10 in THP-1 cells and BMDMs. Cytokine induction by PBP was MyD88-dependent. Removal of PBP from E. chaffeensis lysate using penicillin affinity column and a complementation assay confirmed cytokine-inducing activity of native PBP. CONCLUSIONS: The cytokine-inducing activity by E. chaffeensis PBP provides novel insights into pathogen-associated molecular patterns and pathogenesis of E. chaffeensis infection.