PMID- 22539814 OWN - NLM STAT- MEDLINE DCOM- 20121001 LR - 20211021 IS - 1537-6613 (Electronic) IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 206 IP - 1 DP - 2012 Jul 1 TI - Penicillin-binding protein of Ehrlichia chaffeensis: cytokine induction through MyD88-dependent pathway. PG - 110-6 LID - 10.1093/infdis/jis313 [doi] AB - 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 alpha, interleukin 1beta, 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. FAU - Rahman, Mohd Akhlakur AU - Rahman MA AD - Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210-1093, USA. FAU - Cheng, Zhihui AU - Cheng Z FAU - Matsuo, Junji AU - Matsuo J FAU - Rikihisa, Yasuko AU - Rikihisa Y LA - eng GR - R01 AI047885/AI/NIAID NIH HHS/United States GR - R01AI47885/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120426 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Chemokine CXCL2) RN - 0 (Cytokines) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-8) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Penicillin-Binding Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Cell Line, Tumor MH - Chemokine CXCL2/biosynthesis/genetics/immunology MH - Cytokines/*biosynthesis/genetics/immunology MH - Ehrlichia chaffeensis/genetics/immunology/*metabolism MH - Ehrlichiosis/genetics/metabolism MH - Humans MH - Interleukin-10/biosynthesis/genetics/immunology MH - Interleukin-1beta/biosynthesis/genetics/immunology MH - Interleukin-8/biosynthesis/genetics/immunology MH - Macrophages/immunology/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Monocytes/metabolism MH - Myeloid Differentiation Factor 88/genetics/immunology/*metabolism MH - Penicillin-Binding Proteins/genetics/immunology/*metabolism MH - Tumor Necrosis Factor-alpha/biosynthesis/genetics/immunology PMC - PMC3415931 EDAT- 2012/04/28 06:00 MHDA- 2012/10/02 06:00 PMCR- 2013/07/01 CRDT- 2012/04/28 06:00 PHST- 2012/04/28 06:00 [entrez] PHST- 2012/04/28 06:00 [pubmed] PHST- 2012/10/02 06:00 [medline] PHST- 2013/07/01 00:00 [pmc-release] AID - jis313 [pii] AID - 10.1093/infdis/jis313 [doi] PST - ppublish SO - J Infect Dis. 2012 Jul 1;206(1):110-6. doi: 10.1093/infdis/jis313. Epub 2012 Apr 26.