Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
Inherited IL-12 Unresponsiveness Contributes to the High LPS Resistance of theLpsd C57BL/10ScCr Mouse
Beteiligte:
Merlin, Thomas;
Sing, Andreas;
Nielsen, Peter J.;
Galanos, Chris;
Freudenberg, Marina A.
Erschienen:
The American Association of Immunologists, 2001
Erschienen in:
The Journal of Immunology, 166 (2001) 1, Seite 566-573
Sprache:
Englisch
DOI:
10.4049/jimmunol.166.1.566
ISSN:
0022-1767;
1550-6606
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Lps d mouse strains are characterized by the presence of a defective Lps/tlr4 gene that make them refractory to the biological activity of LPS. One of the mouse strains commonly used to study LPS defects is the C57BL/10ScCr (Cr) strain. However, unlike other Lpsd strains, the Cr strain also has a heavily impaired IFN-γ response to micro-organisms. As a consequence, unlike other Lpsd mouse strains, they do not acquire a partial LPS susceptibility when treated with sensitizing bacteria. Because IL-12 is important for the microbial induction of IFN-γ, we investigated whether the production or function of IL-12 might be defective in Cr mice. IL-12 mRNA (p35 and p40) was present in the spleen of untreated Cr mice, IL-12p40 mRNA was inducible in mice injected with live or killed Salmonella typhimurium, and IL-12 (p70) was inducible in macrophages by bacteria. Thus, Cr mice exhibit normal IL-12 responses. In functional tests, splenocytes of untreated or of S. typhimurium-infected mice failed to produce IFN-γ when stimulated with murine rIL-12 or with a combination of IL-12 and murine rIL-18 or Con A. Furthermore, Cr mice were identical with IL-12p35/p40 and IL-12 receptor β1 knockout mice in their impaired in vivo and in vitro IFN-γ responses to bacteria. Thus, Cr mice carry a second genetic defect unrelated to the Lps/tlr4 mutation that underlies the IL-12 unresponsiveness and contributes to the LPS resistance and impaired innate immune response in this strain.</jats:p>