Defect in macrophage effector function confers Salmonella typhimurium susceptibility on C3H/HeJ mice

Alison D. O'Brien, Eleanor S. Metcalf, David L. Rosenstreich

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Abstract

The defective allele of the endotoxin response locus (Lpsd) renders mice (e.g., C3H/HeJ strain) both endotoxin hyporesponsive and susceptible to Salmonella typhimurium. In this study, the mechanism of Lpsd-regulated susceptibility to murine typhoid was examined. C3H/ HeJ mice became significantly more resistant to S. typhimurium by reconstitution with bone marrow from syngeneic C3H/HeN mice (Lpsn, salmonella resistant). Thus, the Lpsd resistance defect appeared to reside in a radiosensitive bone marrow-derived cell(s). At least one of the abnormal cell types appeared to be a macrophage because C3H/HeJ mice preinfected with Mycobacterium bovis (BCG) were, in contrast to controls, able to restrict early salmonella replication in their spleens and displayed a signficant increase in mean time to death. In contrast, no deficiency in uptake of salmonellae by C3H/HeJ macrophages was observed. These results indicate that the early deaths of C3H/HeJ mice following S. typhimurium challenge reflect a failure of their macrophages to limit the growth of these gram-negative bacteria.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalCellular Immunology
Volume67
Issue number2
DOIs
StatePublished - Mar 1 1982

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ASJC Scopus subject areas

  • Immunology

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