The Mannose Receptor: From Endocytic Receptor and Biomarker to Regulator of (Meta)Inflammation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Nov 1

PMID 34721436

Citations 48

Authors

Hendrik J P van der Zande

Dominik Nitsche

Laura Schlautmann

Bruno Guigas

Sven Burgdorf

Affiliations

Soon will be listed here.

Abstract

The mannose receptor is a member of the C-type lectin (CLEC) family, which can bind and internalize a variety of endogenous and pathogen-associated ligands. Because of these properties, its role in endocytosis as well as antigen processing and presentation has been studied intensively. Recently, it became clear that the mannose receptor can directly influence the activation of various immune cells. Cell-bound mannose receptor expressed by antigen-presenting cells was indeed shown to drive activated T cells towards a tolerogenic phenotype. On the other hand, serum concentrations of a soluble form of the mannose receptor have been reported to be increased in patients suffering from a variety of inflammatory diseases and to correlate with severity of disease. Interestingly, we recently demonstrated that the soluble mannose receptor directly promotes macrophage proinflammatory activation and trigger metaflammation. In this review, we highlight the role of the mannose receptor and other CLECs in regulating the activation of immune cells and in shaping inflammatory responses.

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References

Hatzi K, Nance J, Kroenke M, Bothwell M, Haddad E, Melnick A . BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms. J Exp Med. 2015; 212(4):539-53. PMC: 4387288. DOI: 10.1084/jem.20141380. View

Fan W, Yang X, Huang F, Tong X, Zhu L, Wang S . Identification of CD206 as a potential biomarker of cancer stem-like cells and therapeutic agent in liver cancer. Oncol Lett. 2019; 18(3):3218-3226. PMC: 6704291. DOI: 10.3892/ol.2019.10673. View

Rothstein D, Saito H, Streuli M, Schlossman S, Morimoto C . The alternative splicing of the CD45 tyrosine phosphatase is controlled by negative regulatory trans-acting splicing factors. J Biol Chem. 1992; 267(10):7139-47. View

Obstfeld A, Sugaru E, Thearle M, Francisco A, Gayet C, Ginsberg H . C-C chemokine receptor 2 (CCR2) regulates the hepatic recruitment of myeloid cells that promote obesity-induced hepatic steatosis. Diabetes. 2010; 59(4):916-25. PMC: 2844839. DOI: 10.2337/db09-1403. View

Marodi L, Korchak H, JOHNSTON Jr R . Mechanisms of host defense against Candida species. I. Phagocytosis by monocytes and monocyte-derived macrophages. J Immunol. 1991; 146(8):2783-9. View

Heftdal L, Loft A, Hendricks O, Christiansen A, Schiottz-Christensen B, Arnbak B . Divergent effects on macrophage biomarkers soluble CD163 and CD206 in axial spondyloarthritis. Scand J Clin Lab Invest. 2018; 78(6):483-489. DOI: 10.1080/00365513.2018.1500704. View

Kel J, Oldenampsen J, Luca M, Drijfhout J, Koning F, Nagelkerken L . Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis. Am J Pathol. 2007; 170(1):272-80. PMC: 1762692. DOI: 10.2353/ajpath.2007.060335. View

Hayashida K, Kume N, Murase T, Minami M, Nakagawa D, Inada T . Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are elevated in acute coronary syndrome: a novel marker for early diagnosis. Circulation. 2005; 112(6):812-8. DOI: 10.1161/CIRCULATIONAHA.104.468397. View

Wu X, Zhang J, Ge H, Gupte J, Baribault H, Lee K . Soluble CLEC2 Extracellular Domain Improves Glucose and Lipid Homeostasis by Regulating Liver Kupffer Cell Polarization. EBioMedicine. 2015; 2(3):214-24. PMC: 4489977. DOI: 10.1016/j.ebiom.2015.02.013. View

10.

Taylor P, Gordon S, Martinez-Pomares L . The mannose receptor: linking homeostasis and immunity through sugar recognition. Trends Immunol. 2005; 26(2):104-10. DOI: 10.1016/j.it.2004.12.001. View

11.

Wainszelbaum M, Proctor B, Pontow S, Stahl P, Alejandro Barbieri M . IL4/PGE2 induction of an enlarged early endosomal compartment in mouse macrophages is Rab5-dependent. Exp Cell Res. 2006; 312(12):2238-51. DOI: 10.1016/j.yexcr.2006.03.025. View

12.

Skarpengland T, Skjelland M, Kong X, Skagen K, Holm S, Otterdal K . Increased Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Ischemic Stroke and Transient Ischemic Attack. J Am Heart Assoc. 2018; 7(2). PMC: 5850141. DOI: 10.1161/JAHA.117.006479. View

13.

Kume N, Mitsuoka H, Hayashida K, Tanaka M, Kominami G, Kita T . Soluble lectin-like oxidized LDL receptor-1 (sLOX-1) as a sensitive and specific biomarker for acute coronary syndrome--comparison with other biomarkers. J Cardiol. 2010; 56(2):159-65. DOI: 10.1016/j.jjcc.2010.05.002. View

14.

Westcott D, Delproposto J, Geletka L, Wang T, Singer K, Saltiel A . MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med. 2009; 206(13):3143-56. PMC: 2806469. DOI: 10.1084/jem.20091333. View

15.

Zhao Z, Zhu X, Luo Y, Lin C, Chen L . Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 levels are associated with angiographic coronary lesion complexity in patients with coronary artery disease. Clin Cardiol. 2011; 34(3):172-7. PMC: 6652421. DOI: 10.1002/clc.20847. View

16.

Tanaka M, Ikeda K, Suganami T, Komiya C, Ochi K, Shirakawa I . Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis. Nat Commun. 2014; 5:4982. DOI: 10.1038/ncomms5982. View

17.

Sturge J, Todd S, Kogianni G, McCarthy A, Isacke C . Mannose receptor regulation of macrophage cell migration. J Leukoc Biol. 2007; 82(3):585-93. DOI: 10.1189/jlb.0107053. View

18.

East L, Isacke C . The mannose receptor family. Biochim Biophys Acta. 2002; 1572(2-3):364-86. DOI: 10.1016/s0304-4165(02)00319-7. View

19.

Ichioka M, Suganami T, Tsuda N, Shirakawa I, Hirata Y, Satoh-Asahara N . Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans. Diabetes. 2011; 60(3):819-26. PMC: 3046842. DOI: 10.2337/db10-0864. View

20.

Kreer C, Kuepper J, Zehner M, Quast T, Kolanus W, Schumak B . N-glycosylation converts non-glycoproteins into mannose receptor ligands and reveals antigen-specific T cell responses in vivo. Oncotarget. 2016; 8(4):6857-6872. PMC: 5351675. DOI: 10.18632/oncotarget.14314. View