Mannan-Binding Lectin Regulates Inflammatory Cytokine Production, Proliferation, and Cytotoxicity of Human Peripheral Natural Killer Cells.

Jia Zhou,Jie Li,Daming Zuo,Xiao Lu,Jialiang Luo,Yan Liu,Liyun Zhang,Zhengliang Chen,Mengyao Hu

doi:10.1155/2019/6738286

Abstract

Natural killer (NK) cells represent the founding members of innate lymphoid cells (ILC) and play critical roles in inflammation and the immune response. NK cell effector functions are regulated and fine-tuned by various immune modulators. Mannan (or mannose)-binding lectin (MBL), a soluble C-type lectin, is traditionally recognized as an initiator of the complement pathway. Recently, it is also considered as an immunomodulator by its interaction with kinds of immune cells. However, the effect of MBL on NK cell function remains unexplored. In this study, we found that human plasma MBL could interact directly with peripheral NK cells partially via its collagen-like region (CLR). This MBL binding markedly suppressed the interleukin-2- (IL-2-) induced inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) production but increased the IL-10 production in NK cells. In addition, the expression of activation surface markers such as CD25 and CD69 declined after MBL treatment. Also, MBL impaired the proliferation and lymphokine-activated killing (LAK) of NK cells. Moreover, we demonstrated that MBL inhibited IL-2-induced signal transducers and activators of transcription 5 (STAT5) activation in NK cells. In conclusion, we have uncovered a far unknown regulatory role of MBL on NK cells, a new clue that could be important in the immunomodulatory networks of immune responses.

Highlights

Natural killer (NK) cells belong to the family of innate lymphoid cells (ILC) and play an important arm of the immune system [1]
Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples collected from healthy donors by Ficoll density gradient centrifugation as we reported before [17]
Preincubation of NK cells with collagen-like region (CLR) of MBL before MBL binding significantly attenuated the MBL binding level but neither with Carbohydrate recognition domain CLR (CRD) of MBL nor with mannan (Figures 1(b) and 1(d)). These results indicated that MBL could directly bind to NK cells partially via CLR of MBL

Summary

Introduction

Natural killer (NK) cells belong to the family of innate lymphoid cells (ILC) and play an important arm of the immune system [1]. They can exert their cytotoxicity against the infected, transformed, or otherwise “stressed” cells without presensitization or MHC restriction [2] Their constitutive storage of perforin and granzymes, as well as the rapid production of IFN-γ and TNF-α upon priming, allows their prompt intervention against target cells and the initiation of inflammation [3]. They exhibit their immunomodulatory function, affecting other cells and acting as a link between the adaptive and innate immunity [4]. The mechanisms that control NK cell activity in the immune regulatory networks had not yet been fully understood

Methods

Results

Discussion

Conclusion