CD8+XCR1neg Dendritic Cells Express High Levels of Toll-Like Receptor 5 and a Unique Complement of Endocytic Receptors.

Ben Wylie,Teagan Wagner,Shane R Stone,Mark N Cruickshank,James Read,Anthony C Buzzai,Niamh Troy,Genevieve Syn,Jason Waithman,Anthony Bosco,Bree Foley

doi:10.3389/fimmu.2018.02990

Ben Wylie, Teagan Wagner + Show 9 more

Open Access

https://doi.org/10.3389/fimmu.2018.02990

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Abstract

Conventional dendritic cells (cDC) resident in the lymphoid organs of mice have been classically divided into CD8+ and CD8neg subsets. It is well-established that CD8+ dendritic cells (DCs) and their migratory counterparts in the periphery comprise the cross-presenting cDC1 subset. In contrast, CD8neg DCs are grouped together in the heterogeneous cDC2 subset. CD8neg DCs are relatively poor cross-presenters and drive more prominent CD4+ T cell responses against exogenous antigens. The discovery of the X-C motif chemokine receptor 1 (XCR1) as a specific marker of cross-presenting DCs, has led to the identification of a divergent subset of CD8+ DCs that lacks the ability to cross-present. Here, we report that these poorly characterized CD8+XCR1neg DCs have a gene expression profile that is consistent with both plasmacytoid DCs (pDCs) and cDC2. Our data demonstrate that CD8+XCR1neg DCs possess a unique pattern of endocytic receptors and a restricted toll-like receptor (TLR) profile that is particularly enriched for TLR5, giving them a unique position within the DC immunosurveillance network.

Highlights

Dendritic cells (DCs) play a key role in the immunosurveillance of pathogens and tumors, being specialized in the acquisition and presentation of foreign antigens and the regulation of T cell immunity [1]
The more heterogeneous cDC2 subset was first described in the spleen as being CD4+, reliant on the transcription factor interferon regulatory factor 4 (IRF4) and better equipped to present antigen on major histocompatability complex (MHC) class II [56]
CD4+ DCs are the major population of cDC2 in the spleen, they are less well represented among cDC2 subsets in the lymph nodes, which contain a mix of resident and migratory DCs [55]

Summary

Introduction

Dendritic cells (DCs) play a key role in the immunosurveillance of pathogens and tumors, being specialized in the acquisition and presentation of foreign antigens and the regulation of T cell immunity [1]. CD8+ and CD103+ DCs comprise the cross-presenting cDC1 family [4, 5], which can be identified by expression of the X-C motif chemokine receptor 1 (XCR1) [6, 7]. The primary roles of these DCs are the cross-presentation of viral [8,9,10] and tumor antigens [11], and the maintenance of peripheral tolerance [12,13,14]. PDCs can be distinguished from cDC subsets by their expression of bone marrow stromal antigen 2 (BST2) [20] and sialic acid Plasmacytoid DCs (pDCs) are the third distinct lineage of DCs and are the primary source of type I interferon (IFN) following viral infection [19]. pDCs can be distinguished from cDC subsets by their expression of bone marrow stromal antigen 2 (BST2) [20] and sialic acid

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