Evasion of human innate immunity without antagonizing TLR4 by mutant Salmonella enterica serovar Typhimurium having penta-acylated lipid A.

• Matsuura, Motohiro

• Kawasaki, Kiyoshi

• Kawahara, Kazuyoshi

• Mitsuyama, Masao

Abstract

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.

Journal

• Innate immunity

  Innate immunity 18 (5), 764-773, 2012-10

  SAGE Publications

Keywords

• 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

Details

• CRID: 1050001335786210944
• NII Article ID: 120005398390
• ISSN: 17534259
• HANDLE: 2433/184286
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles
  • KAKEN