Cxxc Finger Protein 1 Positively Regulates GM-CSF-Derived Macrophage Phagocytosis Through Csf2rα-Mediated Signaling.

Zhaoyuan Hui,Yikai Luo,Wei Li,Xia Liu,Shenghui Hong,Jianli Wang,Linrong Lu,Zhonghui Xue,Lina Zhou,Di Wang,Lie Wang,Lingfeng Zhou,Feng Lin

doi:10.3389/fimmu.2018.01885

Abstract

Macrophages have a defensive function against bacteria through phagocytosis and the secretion of cytokines. Histone modifications play an essential role in macrophage functions. Here, we report that Cxxc finger protein 1 (CFP1), a key component of the SETD1 histone methyltransferase complex, promoted the phagocytic and bactericidal activity of GM-CSF-derived macrophages. CFP1-deficient mice were more susceptible to bacterial infection due to the decreased expression of Csf2rα, a subunit of the GM-CSF receptor essential for inflammation and alveolar macrophage development, through the loss of H3K4 modifications in the promoter of the Csf2rα gene. In addition, the lung tissues of CFP1-deficient mice exhibited spontaneous inflammatory symptoms, including both the infiltration of inflammatory cells and the accumulation of surfactant phospholipids and proteins. Furthermore, we showed that Csf2rα and PU.1 can partially rescue the defects in phagocytosis and in the intracellular killing of bacteria. Collectively, our data highlight the importance of CFP1 in the phagocytic and bactericidal activity of macrophages.

Highlights

Innate immunity constitutes the first line of host defense against bacteria and is mediated by phagocytes such as macrophages
We performed qPCR and western blot analyses to detect the deficiency of Cxxc finger protein 1 (CFP1) in GM-CSF-cultured bone marrowderived macrophages, which confirmed that CFP1 was successfully deleted in the CFP1-deficient mice (Figures S1A,B in the Supplementary Material)
There was no significant difference between CFP1-deficient and wild-type mice in the percentage or cell number of F4/80+CD11b+ macrophages and Ly6ChiCD11b+ inflammatory monocytes in the bone marrow (Figure S1C in Supplementary Material) and spleen (Figure S1D in the Supplementary Material)

Summary

Introduction

Innate immunity constitutes the first line of host defense against bacteria and is mediated by phagocytes such as macrophages. As a major type of innate immune cell, macrophages can phagocytose bacteria and secrete both proinflammatory cytokines and antimicrobial mediators [1]. Phagocytes such as macrophages can clear bacteria through phagocytosis, which includes the recognition, uptake, and degradation of bacteria. Phagocytosis has been recognized as a critical component of the innate immune response to bacteria [2]. Histone modifications are important regulators of chromatin function and recruit specific nuclear factors in order to promote different cellular functions. These modifications include the methylation, acetylation, phosphorylation, or ubiquitylation of different

Methods

Results

Conclusion