Characterization of the Interferon-Producing Cell in Mice Infected with Listeria monocytogenes

PLoS Pathogens

Thomas Rülicke¹  Tadatsugu Taniguchi²  Claus Vogl³  Thomas Decker³  Gabriele Stengl⁴  Silvia Stockinger⁵  Benjamin Reutterer⁵  Sandra Westermayer⁵  Andreas Pilz⁵  Didier Soulat⁵  Renate Kastner⁵  Elisabeth Kernbauer⁵  Ulrich Kalinke⁶  Theresa Frenz⁶  Zoe Waibler⁶  Mathias Müller⁷ 

[1] Biomodels Austria, University of Veterinary Medicine, Vienna, Austria;Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan;Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria;Institute of Molecular Pathology, Vienna, Austria;Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria;Paul-Ehrlich-Institut, Langen, Germany;TWINCORE, Centre for Experimental and Clinical Infection Research, Hanover, Germany

关键词: Listeria monocytogenes;    Macrophages;    Spleen;    Bone marrow cells;    Listeria;    RNA extraction;    Lethality (bacteriology);    Immune response;   

DOI  :  10.1371/journal.ppat.1000355

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Production of type I interferons (IFN-I, mainly IFNα and IFNβ) is a hallmark of innate immune responses to all classes of pathogens. When viral infection spreads to lymphoid organs, the majority of systemic IFN-I is produced by a specialized “interferon-producing cell” (IPC) that has been shown to belong to the lineage of plasmacytoid dendritic cells (pDC). It is unclear whether production of systemic IFN-I is generally attributable to pDC irrespective of the nature of the infecting pathogen. We have addressed this question by studying infections of mice with the intracellular bacterium Listeria monocytogenes. Protective innate immunity against this pathogen is weakened by IFN-I activity. In mice infected with L. monocytogenes, systemic IFN-I was amplified via IFN-β, the IFN-I receptor (IFNAR), and transcription factor interferon regulatory factor 7 (IRF7), a molecular circuitry usually characteristic of non-pDC producers. Synthesis of serum IFN-I did not require TLR9. In contrast, in vitro–differentiated pDC infected with L. monocytogenes needed TLR9 to transcribe IFN-I mRNA. Consistent with the assumption that pDC are not the producers of systemic IFN-I, conditional ablation of the IFN-I receptor in mice showed that most systemic IFN-I is produced by myeloid cells. Furthermore, results obtained with FACS-purified splenic cell populations from infected mice confirmed the assumption that a cell type with surface antigens characteristic of macrophages and not of pDC is responsible for bulk IFN-I synthesis. The amount of IFN-I produced in the investigated mouse lines was inversely correlated to the resistance to lethal infection. Based on these data, we propose that the engagement of pDC, the mode of IFN-I mobilization, as well as the shaping of the antimicrobial innate immune response by IFN-I differ between intracellular pathogens.

【 授权许可】

CC BY