Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance.

2.50
Hdl Handle:
http://hdl.handle.net/10033/305989
Title:
Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance.
Authors:
Puttur, Franz; Arnold-Schrauf, Catharina; Lahl, Katharina; Solmaz, Gulhas; Lindenberg, Marc; Mayer, Christian Thomas; Gohmert, Melanie; Swallow, Maxine; van Helt, Christopher; Schmitt, Heike; Nitschke, Lars; Lambrecht, Bart N; Lang, Roland; Messerle, Martin; Sparwasser, Tim ( 0000-0001-5645-902X )
Abstract:
Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon α (IFNα), a critical anti-viral cytokine during the acute phase of murine cytomegalovirus (MCMV) infection. The ligands and biological functions of Siglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC)-transgenic "pDCre" mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing these mice with a Rosa26 reporter strain, a representative fraction of Siglec-H⁺ pDCs is terminally labeled with red fluorescent protein (RFP). Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H during MCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate of pDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced a significant increase in serum IFNα levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNα production, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed further light on pDC biology in future studies.
Affiliation:
Institute for Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research: A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Citation:
Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance. 2013, 9 (9):e1003648 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Sep-2013
URI:
http://hdl.handle.net/10033/305989
DOI:
10.1371/journal.ppat.1003648
PubMed ID:
24086137
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorPuttur, Franzen
dc.contributor.authorArnold-Schrauf, Catharinaen
dc.contributor.authorLahl, Katharinaen
dc.contributor.authorSolmaz, Gulhasen
dc.contributor.authorLindenberg, Marcen
dc.contributor.authorMayer, Christian Thomasen
dc.contributor.authorGohmert, Melanieen
dc.contributor.authorSwallow, Maxineen
dc.contributor.authorvan Helt, Christopheren
dc.contributor.authorSchmitt, Heikeen
dc.contributor.authorNitschke, Larsen
dc.contributor.authorLambrecht, Bart Nen
dc.contributor.authorLang, Rolanden
dc.contributor.authorMesserle, Martinen
dc.contributor.authorSparwasser, Timen
dc.date.accessioned2013-11-29T15:52:34Zen
dc.date.available2013-11-29T15:52:34Zen
dc.date.issued2013-09en
dc.identifier.citationAbsence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance. 2013, 9 (9):e1003648 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid24086137en
dc.identifier.doi10.1371/journal.ppat.1003648en
dc.identifier.urihttp://hdl.handle.net/10033/305989en
dc.description.abstractPlasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H and produce interferon α (IFNα), a critical anti-viral cytokine during the acute phase of murine cytomegalovirus (MCMV) infection. The ligands and biological functions of Siglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC)-transgenic "pDCre" mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing these mice with a Rosa26 reporter strain, a representative fraction of Siglec-H⁺ pDCs is terminally labeled with red fluorescent protein (RFP). Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H during MCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate of pDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced a significant increase in serum IFNα levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNα production, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed further light on pDC biology in future studies.en
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen
dc.titleAbsence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance.en
dc.typeArticleen
dc.contributor.departmentInstitute for Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research: A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.en
dc.identifier.journalPLoS pathogensen

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