The Role of O-Antigen in LPS-Induced Activation of Human NK Cells.

Leonid M Kanevskiy,Rustam H Ziganshin,Elena I Kovalenko,Alexander M Sapozhnikov,William G Telford,Maria A Streltsova,Sofya A Erokhina

doi:10.1155/2019/3062754

Abstract

NK cells can be stimulated by bacterial lipopolysaccharides (LPS). Unlike macrophages, human NK cells do not express or express very low level of surface TLR4 receptor normally required for the LPS stimulation. This has led to the assumption that the mechanisms of stimulating action of LPS on macrophages and NK cells differs. In this work, we investigated the effects of different forms of E. coli LPS, including mutants lacking O-antigen structures, and deacylated LPS on IFNγ production by purified human NK cells. The main findings were the following: (1) NK cells were more sensitive to the S-forms of LPS than the R-forms (LPS lacking O-antigen); (2) LPS triggered a significant increase in IFNγ production by NK cells in concentrations about 1000 times higher than those that can induce cytokine production by macrophages; (3) the composition and structure of saccharide part of LPS have a strong influence on its observed effects on NK cells; and (4) LPS fully retained the ability to trigger cytokine production in NK cells in serum-free media. The acquired data demonstrated that the presence and structure of O-antigen affects the LPS-induced activation of human NK cells.

Highlights

NK cells take part in systemic inflammatory reactions, induced by bacterial lipopolysaccharides, i.e., sepsis
In addition to the activation caused by stimulating interactions with TLR4-bearing cells, NK cells have been shown to be independently activated by bacterial LPS in the presence of cytokines, such as IL-2 [3]
There is evidence that it can be independent of the TLR4 receptor complex on the cell surface [3,4,5], suggesting that conditions of LPS-induced stimulation of NK cells can differ from the classical model

Summary

Introduction

NK cells take part in systemic inflammatory reactions, induced by bacterial lipopolysaccharides, i.e., sepsis (reviewed in [1, 2]). The LPS molecule consists of a lipid moiety, named lipid A, the core oligosaccharide and a polysaccharide tail of inconstant length (O-antigen). The lipid A is a common constituent for all strains of E. coli. It is made up of two glucosamine-phosphates with up to six fatty acid chains attached to both saccharide residues. The core oligosaccharide of E. coli LPS includes the so-called inner core (proximal to the lipid A) and the outer core fragments; it consists of 11-12 monosaccharide residues. There are 5 variants of outer core structures, named R1, R2, R3, R4, and K12, differing between E. coli strains [7]. The O-antigen is polymeric; it usually consists of 10–25 oligosaccharide

Methods

Results

Conclusion