The CD20 homolog Ms4a8a integrates pro‐ and anti‐inflammatory signals in novel M2‐like macrophages and is expressed in parasite infection

Media type: E-Article
Title: The CD20 homolog Ms4a8a integrates pro‐ and anti‐inflammatory signals in novel M2‐like macrophages and is expressed in parasite infection
Contributor: Schmieder, Astrid; Schledzewski, Kai; Michel, Julia; Schönhaar, Kathrin; Morias, Yannick; Bosschaerts, Tom; Van den Bossche, Jan; Dorny, Pierre; Sauer, Andrea; Sticht, Carsten; Géraud, Cyrill; Waibler, Zoe; Beschin, Alain; Goerdt, Sergij
Published: Wiley, 2012
Published in: European Journal of Immunology, 42 (2012) 11, Seite 2971-2982
Language: English
DOI: 10.1002/eji.201142331
ISSN: 0014-2980; 1521-4141
Keywords: Immunology ; Immunology and Allergy
Origination:
Footnote:
Description: <jats:p>Recently, we identified the <jats:styled-content style="fixed-case">CD</jats:styled-content>20 homolog <jats:styled-content style="fixed-case">M</jats:styled-content>s4a8a as a novel molecule expressed by tumor‐associated macrophages that directly enhances tumor growth. Here, we analyzed <jats:styled-content style="fixed-case">M</jats:styled-content>s4a8a<jats:sup>+</jats:sup> macrophages in <jats:styled-content style="fixed-case">M</jats:styled-content>2‐associated infectious pathologies. In late‐stage <jats:italic><jats:styled-content style="fixed-case">T</jats:styled-content>rypanosoma congolense</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">T</jats:styled-content>aenia crassiceps</jats:italic> infections, <jats:styled-content style="fixed-case">M</jats:styled-content>s4a8a expression was detected in hepatic and peritoneal macrophages respectively. Innate immunity in these infections is modulated by <jats:styled-content style="fixed-case">T</jats:styled-content>oll‐like receptor (<jats:styled-content style="fixed-case">TLR</jats:styled-content>) signaling and <jats:styled-content style="fixed-case">TLR</jats:styled-content>2/4/7 agonists strongly induced <jats:styled-content style="fixed-case">M</jats:styled-content>s4a8a expression in bone marrow derived macrophages (<jats:styled-content style="fixed-case">BMDM</jats:styled-content>s) treated with <jats:styled-content style="fixed-case">M</jats:styled-content>2 mediators (glucocorticoids/<jats:styled-content style="fixed-case">IL</jats:styled-content>‐4). <jats:styled-content style="fixed-case">LPS</jats:styled-content>/dexamethasone/<jats:styled-content style="fixed-case">IL</jats:styled-content>‐4‐induced <jats:styled-content style="fixed-case">M</jats:styled-content>s4a8a<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">BMDM</jats:styled-content>s were characterized by strong expression of m<jats:styled-content style="fixed-case">RNA</jats:styled-content> of <jats:italic>mannose receptor</jats:italic> (<jats:italic><jats:styled-content style="fixed-case">M</jats:styled-content>mr</jats:italic>), <jats:italic>arginase 1,</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">CD</jats:styled-content>163,</jats:italic> and by decreased <jats:italic>i<jats:styled-content style="fixed-case">NOS</jats:styled-content></jats:italic> expression. Coinduction of <jats:styled-content style="fixed-case">M</jats:styled-content>s4a8a by <jats:styled-content style="fixed-case">M</jats:styled-content>2 mediators and <jats:styled-content style="fixed-case">TLR</jats:styled-content> agonists involved the classical <jats:styled-content style="fixed-case">TLR</jats:styled-content> signaling cascade via activation of <jats:styled-content style="fixed-case">M</jats:styled-content>y<jats:styled-content style="fixed-case">D</jats:styled-content>88/<jats:styled-content style="fixed-case">TRIF</jats:styled-content> and <jats:styled-content style="fixed-case">NF</jats:styled-content>‐κ<jats:styled-content style="fixed-case">B</jats:styled-content>. Forced overexpression of <jats:styled-content style="fixed-case">M</jats:styled-content>s4a8a modulated the <jats:styled-content style="fixed-case">TLR</jats:styled-content>4 response of <jats:styled-content style="fixed-case">RAW</jats:styled-content>264.7 cells as shown by gene expression profiling. Upregulation of <jats:italic>Hdc, Tcfec,</jats:italic> and <jats:italic>Sla</jats:italic> was confirmed both in primary <jats:styled-content style="fixed-case">LPS</jats:styled-content>/dexamethasone/<jats:styled-content style="fixed-case">IL</jats:styled-content>‐4‐stimulated <jats:styled-content style="fixed-case">M</jats:styled-content>s4a8a<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">BMDM</jats:styled-content>s and in peritoneal macrophages from late‐stage <jats:italic><jats:styled-content style="fixed-case">T</jats:styled-content>aenia crassiceps</jats:italic> infection. In conclusion, we show that <jats:styled-content style="fixed-case">TLR</jats:styled-content> signaling skews the typical alternative macrophage activation program to induce a special <jats:styled-content style="fixed-case">M</jats:styled-content>2‐like macrophage subset in vitro that also occurs in immunomodulatory immune reactions in vivo, a process directly involving the <jats:styled-content style="fixed-case">CD</jats:styled-content>20 homolog <jats:styled-content style="fixed-case">M</jats:styled-content>s4a8a.</jats:p>
Access State: Open Access

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