Details

Autor(en) / Beteiligte

• Hwang, Seung Y.
• Hertzog, Paul J.
• Holland, Kerry A.
• Sumarsono, Sony H.
• Tymms, Martin J.
• Hamilton, John A.
• Whitty, Genevieve
• Bertoncello, Ivan
• Kola, Ismail

Titel

A Null Mutation in the Gene Encoding a Type I Interferon Receptor Component Eliminates Antiproliferative and Antiviral Responses to Interferons α and β and Alters Macrophage responses

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1995-11, Vol.92 (24), p.11284-11288

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1995

Quelle

MEDLINE

Beschreibungen/Notizen

• To examine the in vivo role(s) of type I interferons (IFNs) and to determine the role of a component of the type I IFN receptor (IFNAR1) in mediating responses to these IFNs, we generated mice with a null mutation (-/-) in the IFNAR1 gene. Despite compelling evidence for modulation of cell proliferation and differentiation by type I IFNs, there were no gross signs of abnormal fetal development or morphological changes in adult IFNAR1 -/- mice. However, abnormalities of hemopoietic cells were detected in IFNAR1 -/- mice. Elevated levels of myeloid lineage cells were detected in peripheral blood and bone marrow by staining with Mac-1 and Gr-1 antibodies. Furthermore, bone marrow macrophages from IFNAR1 -/- mice showed abnormal responses to colony-stimulating factor 1 and lipopolysaccharide. IFNAR1 -/- mice were highly susceptible to viral infection: viral titers were undetected 24 hr after infection of IFNAR1 +/+ mice but were extremely high in organs of IFNAR1 -/- mice, demonstrating that the type I IFN system is a major acute antiviral defence. In cell lines derived from IFNAR1 -/- mice, there was no signaling in response to IFN-α or -β as measured by induction of 2'-5' oligoadenylate synthetase, antiviral, or antiproliferative responses. Importantly, these studies demonstrate that type I IFNs function in the development and responses of myeloid lineage cells, particularly macrophages, and that the IFNAR1 receptor component is essential for antiproliferative and antiviral responses to IFN-α and -β.