Induction of IFN-αβ enables Listeria monocytogenes to suppress macrophage activation by IFN-γ
Open Access
- 1 February 2010
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 207 (2), 327-337
- https://doi.org/10.1084/jem.20091746
Abstract
Production of type I interferon (IFN; IFN-alphabeta) increases host susceptibility to Listeria monocytogenes, whereas type II IFN (IFN-gamma) activates macrophages to resist infection. We show that these opposing immunological effects of IFN-alphabeta and IFN-gamma occur because of cross talk between the respective signaling pathways. We found that cultured macrophages infected with L. monocytogenes were refractory to IFN-gamma treatment as a result of down-regulation of the IFN-gamma receptor (IFNGR). The soluble factor responsible for these effects was identified as host IFN-alphabeta. Accordingly, macrophages and dendritic cells (DCs) showed reduced IFNGR1 expression and reduced responsiveness to IFN-gamma during systemic infection of IFN-alphabeta-responsive mice. Furthermore, the increased resistance of mice lacking the IFN-alphabeta receptor (IFNAR(-/-)) to L. monocytogenes correlated with increased expression of IFN-gamma-dependent activation markers by macrophages and DCs and was reversed by depletion of IFN-gamma. Thus, IFN-alphabeta produced in response to bacterial infection and other stimuli antagonizes the host response to IFN-gamma by down-regulating the IFNGR. Such cross talk permits prioritization of IFN-alphabeta-type immune responses and may contribute to the beneficial effects of IFN-beta in treatment of inflammatory diseases such as multiple sclerosis.Keywords
This publication has 43 references indexed in Scilit:
- Type I IFNs mediate development of postinfluenza bacterial pneumonia in miceJCI Insight, 2009
- Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein AJCI Insight, 2009
- Antimicrobial mechanisms of phagocytes and bacterial evasion strategiesNature Reviews Microbiology, 2009
- Life on the inside: the intracellular lifestyle of cytosolic bacteriaNature Reviews Microbiology, 2009
- Regulation of Hierarchical Clustering and Activation of Innate Immune Cells by Dendritic CellsImmunity, 2008
- Distinct TLR- and NLR-Mediated Transcriptional Responses to an Intracellular PathogenPLoS Pathogens, 2008
- Alternative activation of macrophagesNature Reviews Immunology, 2003
- Multiple Defects of Immune Cell Function in Mice with Disrupted Interferon-γ GenesScience, 1993
- Interferon gamma inhibits interleukin 10 production by monocytes.The Journal of Experimental Medicine, 1993
- Contrasting effect of alpha/beta- and gamma-interferons on expression of macrophage Ia antigens.The Journal of Experimental Medicine, 1986