Induction of IFN-αβ enables Listeria monocytogenes to suppress macrophage activation by IFN-γ
| Autor: | Jessica Humann, Manira Rayamajhi, Kristi Penheiter, Laurel L. Lenz, Karl Andreasen |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Immunology
chemical and pharmacologic phenomena Biology medicine.disease_cause Microbiology Interferon-gamma Mice 03 medical and health sciences 0302 clinical medicine Immune system Listeria monocytogenes Interferon medicine Animals Tuberculosis Immunology and Allergy Macrophage Listeriosis Interferon gamma Receptor Receptors Interferon 030304 developmental biology 0303 health sciences Macrophages Brief Definitive Report Receptor Cross-Talk 3. Good health Signal transduction Interferon type I 030215 immunology medicine.drug |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20091746 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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