Macrophages from endotoxin-hyporesponsive (Lps(d)) C3H/HeJ mice are permissive for vesicular stomatitis virus because of reduced levels of endogenous interferon: Possible mechanism for natural resistance to virus infection

S. N. Vogel, D. Fertsch

Research output: Contribution to journalArticle

Abstract

The C3H/HeJ mouse strain bears an autosomal gene defect, Lps(d), which results in a greatly diminished capacity to respond to endotoxin, the ubiquitous lipolysaccharide derived from the cell walls of gram-negative bacteria. These mice also exhibit greater susceptibility to a variety of viral and bacterial infections than syngeneic, fully lipopolysaccharide-responsive (Lps(n)) mouse strains and possess macrophages with defects in differentiation which are reversed by treatment with exogenous interferon (IFN). To test directly the hypothesis that C3H/HeJ macrophages are deficient in endogenous IFN levels, macrophages from C3H/HeJ (Lps(d)) and C3H/OuJ (Lps(n)) mice were compared for sensitivity to vesicular stomatitis virus. At a multiplicity of infection of 0.1, C3H/OuJ macrophages were completely refractory to infection, whereas C3H/HeJ macrophages were permissive for replication, and infection resulted in 100% cytopathic effect. These findings were confirmed with a second inbred Lps(n) and Lps(d) strain pair. Levels of 2',5'-oligoadenylate synthetase were significantly higher in Lps(n) cells. C3H/HeJ macrophages, derived from bone marrow precursors under the influence of macrophage colony-stimulating factor, show previously to induce IFN in macrophages, were as refractory as C3H/OuJ macrophages. Exposure of nonpermissive macrophages to anti-IFN-α/β antibody prior to infection rendered cells permissive. Our findings suggest that endotoxin provides a primary stimulus for the maintenance of normal macrophage differentiation and innate resistance via the induction of endogenous IFN by macrophages.

Original languageEnglish (US)
Pages (from-to)812-818
Number of pages7
JournalJournal of virology
Volume61
Issue number3
DOIs
StatePublished - Jan 1 1987

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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