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

Schleicher U, Liese J, Justies N, Mischke T, Haeberlein S, Sebald H, Kalinke U, Weiss S, Bogdan C (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 9

DOI: 10.3389/fimmu.2018.00079

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.

Authors with CRIS profile

Ulrike Schleicher Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Thomas Mischke Medizinische Fakultät Christian Bogdan Lehrstuhl für Mikrobiologie und Infektionsimmunologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Universitätsklinikum Freiburg DE Germany (DE) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE)

How to cite

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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