Type I Interferon Signaling Is Required for CpG-Oligodesoxynucleotide-Induced Control ofLeishmania major, but Not for Spontaneous Cure of Subcutaneous Primary or SecondaryL. majorInfection

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Details zur Publikation

Autorinnen und Autoren: Schleicher U, Liese J, Justies N, Mischke T, Haeberlein S, Sebald H, Kalinke U, Weiss S, Bogdan C
Zeitschrift: Frontiers in Immunology
Jahr der Veröffentlichung: 2018
Band: 9
ISSN: 1664-3224


Abstract

We previously showed that in mice infected withLeishmania majortype I interferons (IFNs) initiate the innate immune response to the parasite at day 1 and 2 of infection. Here, we investigated which type I IFN subtypes are expressed during the first 8 weeks ofL. majorinfection and whether type I IFNs are essential for a protective immune response and clinical cure of the disease. In self-healing C57BL/6 mice infected with a high dose ofL. major, IFN-α4, IFN-α5, IFN-α11, IFN-α13, and IFN-β mRNA were most prominently regulated during the course of infection. In C57BL/6 mice deficient for IFN-β or the IFN-α/β-receptor chain 1 (IFNAR1), development of skin lesions and parasite loads in skin, draining lymph node, and spleen was indistinguishable from wild-type (WT) mice. In line with the clinical findings, C57BL/6 IFN-β-/-, IFNAR1-/-, and WT mice exhibited similar mRNA expression levels of IFN-γ, interleukin (IL)-4, IL-12, IL-13, inducible nitric oxide synthase, and arginase 1 during the acute and late phase of the infection. Also, myeloid dendritic cells from WT and IFNAR1-/-mice produced comparable amounts of IL-12p40/p70 protein upon exposure toL. major in vitro. In non-healing BALB/c WT mice, the mRNAs of IFN-α subtypes (α2, α4, α5, α6, and α9) were rapidly induced after high-doseL. majorinfection. However, genetic deletion of IFNAR1 or IFN-β did not alter the progressive course of infection seen in WT BALB/c mice. Finally, we tested whether type I IFNs and/or IL-12 are required for the prophylactic effect of CpG-oligodesoxynucleotides (ODN) in BALB/c mice. Local and systemic administration of CpG-ODN 1668 protected WT and IFN-β-/-mice equally well from progressive leishmaniasis. By contrast, the protective effect of CpG-ODN 1668 was lost in BALB/c IFNAR1-/-(despite a sustained suppression of IL-4) and in BALB/c IL-12p35-/-mice. From these data, we conclude that IFN-β and IFNAR1 signaling are dispensable for a curative immune response toL. majorin C57BL/6 mice and irrelevant for disease development in BALB/c mice, whereas IL-12 and IFN-α subtypes are essential for the disease prevention by CpG-ODNs in this mouse strain.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Bogdan, Christian Prof. Dr.
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Mischke, Thomas
Medizinische Fakultät
Schleicher, Ulrike PD Dr.
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene


Einrichtungen weiterer Autorinnen und Autoren

Helmholtz-Zentrum für Infektionsforschung (HZI)
Universitätsklinikum Freiburg


Zitierweisen

APA:
Schleicher, U., Liese, J., Justies, N., Mischke, T., Haeberlein, S., Sebald, H.,... Bogdan, C. (2018). Type I Interferon Signaling Is Required for CpG-Oligodesoxynucleotide-Induced Control ofLeishmania major, but Not for Spontaneous Cure of Subcutaneous Primary or SecondaryL. majorInfection. Frontiers in Immunology, 9. https://dx.doi.org/10.3389/fimmu.2018.00079

MLA:
Schleicher, Ulrike, et al. "Type I Interferon Signaling Is Required for CpG-Oligodesoxynucleotide-Induced Control ofLeishmania major, but Not for Spontaneous Cure of Subcutaneous Primary or SecondaryL. majorInfection." Frontiers in Immunology 9 (2018).

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Zuletzt aktualisiert 2019-17-04 um 08:17