title: Essential role of toll-like receptor 4 in Acinetobacter baumannii-induced immune responses in immune cells.
abstract: TLR4 is a membrane sensor for lipopolysaccharide (LPS), a major cell wall component of gram-negative bacteria. In this study, we investigated the role of TLR4 on innate immune responses in immune cells against Acinetobacter baumannii. Bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs) were isolated from WT and TLR4-deficient mice and infected with A. baumannii ATCC 15150. ELISA assay revealed that the production of IL-6 and TNF-α by A. baumannii was impaired in TLR4-deficient macrophages. However, absence of TLR2 did not affect A. baumannii-induced cytokines production in BMDMs. In addition, TLR4 was required for the optimal production of IL-6, TNF-α, and IL-12 in BMDCs in response to A. baumannii. Western blot analysis showed that A. baumannii leads to the activation of NF-κB and MAPKs (p38, ERK, and JNK) in macrophages via TLR4-dependent pathway. mRNA expression of iNOS and NO production was elicited in WT BMDMs in response to A. baumannii, which was abolished in TLR4-deficienct cells. Bacterial killing ability against A. baumannii was impaired in TLR4-deficient BMDMs. In addition, A. baumannii induced apoptosis in BMDMs via TLR4-independent pathway. Our results demonstrate that TLR4 is essential for initiating innate immune response of macrophages against A. baumannii infection.
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Kim
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Junglim
authors.initials: J
authors.lastname: Lee
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeon
authors.forename: Se-Ra
authors.initials: SR
authors.lastname: Park
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kang
authors.forename: Jae-Hak
authors.initials: JH
authors.lastname: Park
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
mesh_terms: D040981:Acinetobacter baumannii / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D020929:Mitogen-Activated Protein Kinase Kinases