PMID- 22982140 OWN - NLM STAT- MEDLINE DCOM- 20130529 LR - 20181202 IS - 1096-1208 (Electronic) IS - 0882-4010 (Linking) VI - 54 DP - 2013 Jan TI - Essential role of toll-like receptor 4 in Acinetobacter baumannii-induced immune responses in immune cells. PG - 20-5 LID - S0882-4010(12)00160-X [pii] LID - 10.1016/j.micpath.2012.08.008 [doi] AB - 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-alpha 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-alpha, and IL-12 in BMDCs in response to A. baumannii. Western blot analysis showed that A. baumannii leads to the activation of NF-kappaB 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. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Kim, Chang-Hwan AU - Kim CH AD - Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 151-742, Republic of Korea. FAU - Jeong, Yu-Jin AU - Jeong YJ FAU - Lee, Junglim AU - Lee J FAU - Jeon, Soo-Jin AU - Jeon SJ FAU - Park, Se-Ra AU - Park SR FAU - Kang, Min-Jung AU - Kang MJ FAU - Park, Jae-Hak AU - Park JH FAU - Park, Jong-Hwan AU - Park JH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120912 PL - England TA - Microb Pathog JT - Microbial pathogenesis JID - 8606191 RN - 0 (Interleukin-6) RN - 0 (NF-kappa B) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 187348-17-0 (Interleukin-12) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) SB - IM MH - Acinetobacter baumannii/*immunology MH - Animals MH - Apoptosis MH - Blotting, Western MH - Cells, Cultured MH - Dendritic Cells/*immunology/microbiology MH - Enzyme-Linked Immunosorbent Assay MH - Gene Expression Profiling MH - Interleukin-12/metabolism MH - Interleukin-6/metabolism MH - Macrophages/*immunology/microbiology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mitogen-Activated Protein Kinase Kinases/biosynthesis MH - NF-kappa B/biosynthesis MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type II/biosynthesis MH - Toll-Like Receptor 4/deficiency/*immunology MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2012/09/18 06:00 MHDA- 2013/05/31 06:00 CRDT- 2012/09/18 06:00 PHST- 2012/05/17 00:00 [received] PHST- 2012/08/28 00:00 [revised] PHST- 2012/08/29 00:00 [accepted] PHST- 2012/09/18 06:00 [entrez] PHST- 2012/09/18 06:00 [pubmed] PHST- 2013/05/31 06:00 [medline] AID - S0882-4010(12)00160-X [pii] AID - 10.1016/j.micpath.2012.08.008 [doi] PST - ppublish SO - Microb Pathog. 2013 Jan;54:20-5. doi: 10.1016/j.micpath.2012.08.008. Epub 2012 Sep 12.