Memory-Like Antigen-Specific Human NK Cells from TB Pleural Fluids Produced IL-22 in Response to IL-15 or Mycobacterium tuberculosis Antigens.

Xiaoying Fu,Changyou Wu,Sifei Yu,Suihua Lao,Baiqing Li,Binyan Yang,Niklas K Björkström

doi:10.1371/journal.pone.0151721

Xiaoying Fu, Changyou Wu + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0151721

Copy DOI

Abstract

Our previous result indicated that memory-like human natural killer (NK) cells from TB pleural fluid cells (PFCs) produced large amounts of IFN-γ in response to Bacille Calmette Guerin (BCG). Furthermore, recent studies have shown that human lymphoid tissues harbored a unique NK cell subset that specialized in production of interleukin (IL)-22, a proinflammatory cytokine that mediates host defense against pathogens. Yet little information was available with regard to the properties of IL-22 production by memory-like human NK cells. In the present study, we found that cytokines IL-15 induced and IL-12 enhanced the levels of IL-22 by NK cells from TB PFCs. In addition, IL-22 but not IL-17 was produced by NK cells from PFCs in response to BCG and M.tb-related Ags. More importantly, the subset of specific IL-22-producing NK cells were distinct from IFN-γ-producing NK cells in PFCs. CD45RO+ or CD45RO- NK cells were sorted, co-cultured with autologous monocytes and stimulated with BCG for the production of IL-22. The result demonstrated that CD45RO+ but not CD45RO- NK cells produced significantly higher level of IL-22. Anti-IL-12Rβ1 mAbs (2B10) partially inhibit the expression of IL-22 by NK cells under the culture with BCG. Consistently, BCG specific IL-22-producing NK cells from PFCs expressed CD45ROhighNKG2Dhighgranzyme Bhigh. In conclusion, our data demonstrated that memory-like antigen-specific CD45RO+ NK cells might participate in the recall immune response for M. tb infection via producing IL-22, which display a critical role to fight against M. tb.

Highlights

Tuberculosis (TB) remains a leading cause of mortality worldwide [1]
To detect whether IL-15 or IL-12 had any effect on the production of IL-22 from peripheral blood mononuclear cells (PBMCs), we stimulated PBMCs 48–72 h with various concentrations of IL-15 or IL-12 and the levels of IL22 in the cell-free culture supernatants were assessed by ELISA
The results showed that natural killer (NK) cells from pleural fluid cells (PFCs) expressed significantly higher levels of IL-22 compared with NK cells from PBMCs (0.15%±0.06% vs 0.06%±0.009%) in response to IL-15 but not IL12

Summary

Introduction

Tuberculosis (TB) remains a leading cause of mortality worldwide [1]. the risk of developing active tuberculosis was aggravated by a variety of insufficient prevention efforts, such as HIV infection, diabetes, drug-resistant strains of mycobacterium tuberculosis and immunosuppressant treatment [2,3,4]. Tuberculous pleurisy is a good model for the study of TB specific cells [5,6]. Both innate and adaptive immune systems contribute to host defense against infection with M. tb [7,8,9,10,11,12,13]. Recent studies have found that human NK cells produce IFN-γ and IL-22, which display an important role in host defense and homeostasis, and are critical for induction of antimicrobial peptides in response to bacterial infections [18]. NK-IL-22 cells provide an innate source of IL-22 that may help constrain inflammation and protect mucosal sites [18,24]

Methods

Results

Conclusion