PMID- 22806454 OWN - NLM STAT- MEDLINE DCOM- 20130328 LR - 20211203 IS - 1521-4141 (Electronic) IS - 0014-2980 (Linking) VI - 42 IP - 11 DP - 2012 Nov TI - The CD20 homolog Ms4a8a integrates pro- and anti-inflammatory signals in novel M2-like macrophages and is expressed in parasite infection. PG - 2971-82 LID - 10.1002/eji.201142331 [doi] AB - Recently, we identified the CD20 homolog Ms4a8a as a novel molecule expressed by tumor-associated macrophages that directly enhances tumor growth. Here, we analyzed Ms4a8a(+) macrophages in M2-associated infectious pathologies. In late-stage Trypanosoma congolense and Taenia crassiceps infections, Ms4a8a expression was detected in hepatic and peritoneal macrophages respectively. Innate immunity in these infections is modulated by Toll-like receptor (TLR) signaling and TLR2/4/7 agonists strongly induced Ms4a8a expression in bone marrow derived macrophages (BMDMs) treated with M2 mediators (glucocorticoids/IL-4). LPS/dexamethasone/IL-4-induced Ms4a8a(+) BMDMs were characterized by strong expression of mRNA of mannose receptor (Mmr), arginase 1, and CD163, and by decreased iNOS expression. Coinduction of Ms4a8a by M2 mediators and TLR agonists involved the classical TLR signaling cascade via activation of MyD88/TRIF and NF-kappaB. Forced overexpression of Ms4a8a modulated the TLR4 response of RAW264.7 cells as shown by gene expression profiling. Upregulation of Hdc, Tcfec, and Sla was confirmed both in primary LPS/dexamethasone/IL-4-stimulated Ms4a8a(+) BMDMs and in peritoneal macrophages from late-stage Taenia crassiceps infection. In conclusion, we show that TLR signaling skews the typical alternative macrophage activation program to induce a special M2-like macrophage subset in vitro that also occurs in immunomodulatory immune reactions in vivo, a process directly involving the CD20 homolog Ms4a8a. CI - (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Schmieder, Astrid AU - Schmieder A AD - Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. astrid.schmieder@umm.de FAU - Schledzewski, Kai AU - Schledzewski K FAU - Michel, Julia AU - Michel J FAU - Schonhaar, Kathrin AU - Schonhaar K FAU - Morias, Yannick AU - Morias Y FAU - Bosschaerts, Tom AU - Bosschaerts T FAU - Van den Bossche, Jan AU - Van den Bossche J FAU - Dorny, Pierre AU - Dorny P FAU - Sauer, Andrea AU - Sauer A FAU - Sticht, Carsten AU - Sticht C FAU - Geraud, Cyrill AU - Geraud C FAU - Waibler, Zoe AU - Waibler Z FAU - Beschin, Alain AU - Beschin A FAU - Goerdt, Sergij AU - Goerdt S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120905 PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Antigens, CD) RN - 0 (Antigens, CD20) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD163 antigen) RN - 0 (Lectins, C-Type) RN - 0 (Mannose Receptor) RN - 0 (Mannose-Binding Lectins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cell Surface) RN - 0 (Toll-Like Receptors) RN - 63231-63-0 (RNA) RN - EC 3.5.3.1 (Arg1 protein, mouse) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Animals MH - Antigens, CD/genetics/immunology MH - Antigens, CD20/*immunology MH - Antigens, Differentiation, Myelomonocytic/genetics/immunology MH - Arginase/genetics/immunology MH - Cell Line MH - Immunity, Innate/immunology MH - Lectins, C-Type/genetics/immunology MH - Macrophage Activation/immunology MH - Macrophages/*immunology/parasitology MH - Mannose Receptor MH - Mannose-Binding Lectins/genetics/immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Oligonucleotide Array Sequence Analysis MH - RNA/chemistry/genetics MH - RNA, Messenger/chemistry/genetics MH - Receptors, Cell Surface/genetics/immunology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/immunology MH - Specific Pathogen-Free Organisms MH - Taenia/*immunology MH - Taeniasis/*immunology/parasitology MH - Toll-Like Receptors/agonists MH - Trypanosoma congolense/*immunology MH - Trypanosomiasis, African/*immunology/parasitology EDAT- 2012/07/19 06:00 MHDA- 2013/03/30 06:00 CRDT- 2012/07/19 06:00 PHST- 2011/12/14 00:00 [received] PHST- 2012/06/14 00:00 [revised] PHST- 2012/07/10 00:00 [accepted] PHST- 2012/07/19 06:00 [entrez] PHST- 2012/07/19 06:00 [pubmed] PHST- 2013/03/30 06:00 [medline] AID - 10.1002/eji.201142331 [doi] PST - ppublish SO - Eur J Immunol. 2012 Nov;42(11):2971-82. doi: 10.1002/eji.201142331. Epub 2012 Sep 5.