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

Abstract

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.

CD81 Controls Immunity to Listeria Infection through Rac-Dependent Inhibition of Proinflammatory Mediator Release and Activation of Cytotoxic T Cells

“…The main mechanism described to this harmful role relies on the induction of apoptosis, particularly of lymphocytes as well as macrophages (47,48). It has been shown, using IFN-b reporter mice, that Tip-DCs are an important source of IFN-b during Listeria infection (49) as are CD11b + DCs (50). This finding might suggest that type I IFN production can act as a mechanism of selfregulation by immune cells, which could be subverted by Listeria for its own profit.…”

LipA, a Tyrosine and Lipid Phosphatase Involved in the Virulence of Listeria monocytogenes

“…Animal experiments were discussed and approved by the University of Veterinary Medicine Vienna institutional ethics committee and carried out in accordance with protocols approved by the Austrian law (GZ 680 205/67-BrGt/2003). Bacteria were prepared for infection as described previously (52). For infection with the L. monocytogenes LO28, ⌬lipA, or ⌬lipA::lipA strain, bacteria were washed with PBS (endotoxin free; Sigma) and injected into the peritoneum of 8-to 10-week-old C57BL/6 mice (Charles River).…”

Concomitant type I IFN receptor‐triggering of T cells and of DC is required to promote maximal modified vaccinia virus Ankara‐induced T‐cell expansion

“…To exploit the impact of antigen-presenting cells, we studied conditional mice with a selective IFNAR deletion of myeloid cells (LysM-Cre 1/À IFNAR flox/flox , IFNAR-M) [27,28] or of DC (CD11c-Cre 1/À IFNAR flox/flox , IFNAR-DC). To this end, C57BL/6, IFNAR À/À , IFNAR-M, and IFNAR-DC mice were MVA challenged and the expansion of endogenous B8R-specific CD8 1 T cells was determined.…”