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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.

journal_name

Microb Pathog

journal_title

Microbial pathogenesis

authors

Kim CH,Jeong YJ,Lee J,Jeon SJ,Park SR,Kang MJ,Park JH,Park JH

doi

10.1016/j.micpath.2012.08.008

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

20-5

eissn

0882-4010

issn

1096-1208

pii

S0882-4010(12)00160-X

journal_volume

54

pub_type

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