Selective DNAM-1 expression on small peritoneal macrophages contributes to CD4+ T cell costimulation

Eri Takenaka,Yumi Yamashita-Kanemaru,Kazuko Shibuya,Anh Van Vo,Akira Shibuya

doi:10.1038/s41598-018-33437-4

Eri Takenaka, Yumi Yamashita-Kanemaru + Show 3 more

Open Access

https://doi.org/10.1038/s41598-018-33437-4

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Journal: Scientific Reports	Publication Date: Oct 12, 2018
Citations: 20	License type: open-access

Affiliation: University of Tsukuba

Abstract

Mouse peritoneal macrophages consist of two subsets: large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs), defined as CD11bhiF4/80hi and CD11b+F4/80lo cells, respectively. We reveal that SPMs, but not LPMs, have the ability to present antigens to naïve CD4+ T cells. Coculture of SPMs with naïve ovalbumin (OVA) specific CD4+ T cells (OT-II) in the presence of OVA peptide effectively induced CD4+ T cells priming. SPMs, but not LPMs, strongly express DNAM-1, an activating immunoreceptor. Although antigen uptake and processing were comparable between WT and DNAM-1-deficient SPMs, deficiency of DNAM-1 on SPMs or blockade of DNAM-1 and its ligand interaction impaired CD4+ T cells priming by SPMs. Furthermore, T and B cell responses in mediastinal lymph nodes of mice intraperitoneally immunized with trinitrophenyl (TNP)–OVA protein in Alum adjuvant were enhanced by intraperitoneally transferred wild-type, but not DNAM-1-deficient, SPMs. We propose that SPMs are functionally distinct from LPMs, and DNAM-1 plays a costimulatory role in antigen presentation by SPMs.

Highlights

In the past decade, the importance of distinguishing heterogeneous populations of tissue macrophages on the basis of surface molecules and functions has been recognized[1,2]
Cd266−/− small peritoneal macrophages (SPMs) were transferred into Cd155−/− OT-II mice, the proliferation of both genotypes of SPM showed comparable (Supplementary Fig. 2). These results indicate that the interaction between DNAM-1 on SPMs and CD155 on CD4+ T cells contributes to T cells priming in the draining lymph nodes after antigen immunization via the peritoneal cavity
Previous reports demonstrated that peritoneal macrophages engulf pathogens, induce neutrophils recruitment into the peritoneal cavity and play important roles in the control of infections[23,24,25]; the macrophages analyzed in these reports are likely large peritoneal macrophages (LPMs) on the basis of their surface markers

Summary

Introduction

The importance of distinguishing heterogeneous populations of tissue macrophages on the basis of surface molecules and functions has been recognized[1,2]. Inflammatory monocytes infiltrate into the peritoneal cavity and may differentiate into SPMs3. Both SPMs and LPMs show phagocytic ability; phagocytic activity against bacteria[3] and zymosan[9] is higher in SPMs than LPMs, whereas phagocytic activity against apoptotic cells is lower in SPMs than LPMs7. The DNAX accessory molecule-1 (DNAM-1, known as CD226) is a member of the immunoglobulin superfamily and is constitutively expressed on the majority of NK cells, CD8+ T cells, CD4+ T cells, monocytes, and platelets in both human and mouse[10,11]. We further explored that DNAM-1 is highly expressed on SPMs, but not LPMs and play a costimulatory role in antigen presentation to CD4+ T cells by SPMs

Methods

Results

Conclusion