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Antagonistic crosstalk between type I and II interferons and increased host susceptibility to bacterial infections.
- Source :
-
Virulence [Virulence] 2010 Sep-Oct; Vol. 1 (5), pp. 418-22. - Publication Year :
- 2010
-
Abstract
- Type I and II interferons (IFNs αβ and γ) have opposing effects on immune resistance to certain pathogenic bacteria. While IFNγ generally plays a protective role, IFNαβ exacerbates Listeria monocytogenes and Mycobacterium tuberculosis infections. Our findings provided evidence that this increased susceptibility reflects a novel antagonistic cross talk between IFNαβ and IFNγ. Macrophages infected with L. monocytogenes strains that induce IFNαβ production responded poorly to IFNγ, as measured by reduced phosphorylation of STAT1 and reduced IFNγ-dependent gene expression. The impaired responsiveness to IFNγ correlated with reduced expression of its receptor, IFNGR, by both infected and bystander macrophages. Down regulation of IFNGR was dependent on responsiveness to IFNγ and mimicked by recombinant IFNβ. Mice lacking responsiveness to IFNαβ (IFNAR1 (-/-)) retained high IFNGR expression, developed higher expression of MHC-II on macrophages and DCs, and were more resistant to systemic L. monocytogenes infection--but only in the presence of IFNγ. Thus, the ability of IFNαβ to down regulate IFNGR provides an explanation for its ability to reduce responsiveness to IFNγ and to increase host susceptibility to bacterial infection. It remains to be determined whether and how such antagonistic interferon crosstalk benefits the host.
- Subjects :
- Animals
Dendritic Cells immunology
Gene Expression Profiling
Histocompatibility Antigens Class II biosynthesis
Macrophages immunology
Mice
Phosphorylation
Receptors, Interferon biosynthesis
STAT1 Transcription Factor metabolism
Interferon gamma Receptor
Interferon-alpha immunology
Interferon-beta immunology
Interferon-gamma immunology
Listeria monocytogenes immunology
Macrophages microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 2150-5608
- Volume :
- 1
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Virulence
- Publication Type :
- Academic Journal
- Accession number :
- 21178482
- Full Text :
- https://doi.org/10.4161/viru.1.5.12787