Natural Killer Cells Regulate Pulmonary Macrophages Polarization in Host Defense Against Chlamydial Respiratory Infection.

Lei Zhao,Xiaoqing Zhou,Qianqian Pan,Hong Wang,Weiming Zhao,Jing Li,Xi Yang

doi:10.3389/fcimb.2021.775663

Abstract

NK cells and pulmonary macrophages both are important components of innate immunity. The interaction between NK cells and pulmonary macrophages during chlamydial infection is poorly understood. In this study, we explored the effect of NK cells on regulation of pulmonary macrophage function during chlamydial respiratory infection. We found that NK depletion led to polarization of pulmonary macrophages from M1 to M2 phenotype, and it is related to reduced miR-155 expression in lung macrophage. Using adoptive transfer approach, we found that the recipients receiving lung macrophages isolated from C. muridarum-infected NK-cell-depleted mice exhibited an increased bacterial load and severe inflammation in the lung upon chlamydial challenge infection when compared with the recipients of lung macrophages from infected isotype control antibody treated mice. Herein, the effects of NK cells on macrophage polarization were examined in vitro. We found that NK cells from chlamydial-infected mice (iNK) significantly induced M1 polarization compared to that from uninfected mice (uNK). Inhibition of miR-155 expression in macrophages reduced M1 polarization induced by iNK, while miR-155 over-expression enhanced it. Furthermore, neutralization of IFN-γ in the coculture system decreased the expression of miR-155 by macrophages, and resulted in weakened M1 polarization. The data indicates that NK cells promote M1 polarization through up-regulation of miR-155 in macrophages by producing IFN-γ during chlamydial infection, and NK-regulated macrophage polarization is functionally relevant to host defense against the infection.

Highlights

Chlamydia, as an obligate intracellular bacterium, causes a wide variety of human and animal diseases including ocular, pulmonary, and genital infections (Brunham and Rey-Ladino, 2005)
We found that NK cells had a significant promoting effect on the function of pulmonary macrophage, as shown by enhancing M1 polarization and proinflammatory cytokine production by macrophages, which eventually improved the protection against C. muridarum challenge infection induced by macrophages transfer
Further analysis showed that M1 polarization inhibited by NK depletion was related to decreased expression of miR-155 in lung macrophages

Summary

Introduction

As an obligate intracellular bacterium, causes a wide variety of human and animal diseases including ocular, pulmonary, and genital infections (Brunham and Rey-Ladino, 2005). A limited number of in vivo studies explored the role of macrophages in chlamydial infection (Rothfuchs et al, 2004; Qiu et al, 2008; Prantner et al, 2009; Miyairi et al, 2011; Gracey et al, 2015). In vivo adoptive transfer of macrophages into RAG-1-/-/IFN-g-/- mice resulted in effective control of chlamydial lung infection (Rothfuchs et al, 2004). These researches imply that macrophages can provide protective immunity against chlamydial infection, the underlying mechanism is not yet fully illustrated. It had been reported that in vitro chlamydial infection triggered pro-inflammatory M1 phenotype (Duncan et al, 2020), and M1 macrophages restricted the growth of C. trachomatis, while M2 macrophages

Methods

Results

Conclusion