Evasion of human innate immunity without antagonizing TLR4 by mutant Salmonella enterica serovar Typhimurium having penta-acylated lipid A.
抄録
Modification of a lipid A moiety in Gram-negative bacterial LPS to a less acylated form is thought to facilitate bacterial evasion of host innate immunity, thereby enhancing pathogenicity. The contribution of less-acylated lipid A to interactions of whole bacterial cells with host cells (especially in humans) remains unclear. Mutant strains of Salmonella enterica serovar Typhimurium with fewer acylated groups were generated. The major lipid A form in wild-type (WT) and the mutant KCS237 strain is hexa-acylated; in mutant strains KCS311 and KCS324 it is penta-acylated; and in KCS369 it is tetra-acylated. WT and KCS237 formalin-killed and live bacteria, as well as their LPS, strongly stimulated production of pro-inflammatory cytokines in human U937 cells; this stimulation was suppressed by TLR4 suppressors. LPS of other mutants produced no agonistic activity, but strong antagonistic activity, while their formalin-killed and live bacteria preparations had weak agonistic and no antagonistic activity. Moreover, these less-acylated mutants had increased resistance to phagocytosis by U937 cells. Our results indicate that a decrease of one acyl group (from six to five) is enough to allow Salmonella to evade human innate immunity and that the antagonistic activity of less-acylated lipid A is not utilized for this evasion.
収録刊行物
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- Innate immunity
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Innate immunity 18 (5), 764-773, 2012-10
SAGE Publications
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キーワード
- Bacterial evasion
- human innate immunity
- lipopolysaccharide
- penta-acylated lipid A
- Salmonella
- Acetylation
- Antibodies, Blocking/pharmacology
- Cytokines/metabolism
- Humans
- Immune Evasion
- Immunity, Innate
- Inflammation Mediators/metabolism
- Lipid A/genetics
- Lipid A/metabolism
- Macrophage Activation/drug effects
- Macrophages/drug effects
- Macrophages/immunology
- Mutation/genetics
- Salmonella typhi/immunology
- Salmonella typhi/pathogenicity
- Toll-Like Receptor 4/metabolism
- Typhoid Fever/immunology
- U937 Cells
詳細情報 詳細情報について
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- CRID
- 1050001335786210944
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- NII論文ID
- 120005398390
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- ISSN
- 17534259
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- HANDLE
- 2433/184286
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- CiNii Articles
- KAKEN