THE C3HeB/FeJ MOUSE, A STRAIN IN THE C3H LINEAGE WHICH SEPARATES SALMONELLA SUSCEPTIBILITY AND IMMUNIZABILITY FROM MITOGENIC RESPONSIVENESS TO LIPOPOLYSACCHARIDE

Eisenstein, Toby K.; Deakins, L. W.; Sultzer, Barnet M.

doi:10.1016/b978-0-12-647680-4.50019-8

Cited by 4 publications

(1 citation statement)

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“…At least five different gene loci have been identified. Three of these genes (ity, lps, and the susceptibility gene of C3Heb/FeJ) are expressed during the early phase of infection (10,11,23,30,31,51), and the other two (xid and the late-phase susceptibility gene) are expressed in the later phase of the infection (18,32,43). In comparison with the ity r genotype, the ity s genotype is characterized by a lower intracellular killing rate for both macrophages and granulocytes (23,49,50).…”

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Susceptibility of lipopolysaccharide-responsive and -hyporesponsive ItyS Mice to infection with rough mutants of Salmonella typhimurium

et al. 1996

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The R5 (chemotype Rb) but not the R10 (chemotype Rd) mutant of murine pathogen Salmonella typhimurium 395MS was extremely virulent in intraperitoneal infections of C57BL/10ScCr mice carrying the ity s and lps d alleles. C57BL/6J (ity s lps n) and C3H/HeJ (ity r lps d) mice showed a much higher resistance to the R5 mutant. Further studies were performed with peritoneal macrophages in vitro in order to elucidate susceptibility in lipopolysaccharide (LPS)-hyporesponsive mice carrying Ity s. The intracellular killing capacity of the Ity s Lps d macrophages was lower than that of the Ity s Lps n macrophages for the R5 mutant and may partly explain the increased susceptibility of the Ity s Lps d mice. The deep rough mutant, R10, was rapidly killed intracellularly by the Ity s Lps d macrophages. Processing of the bacteria in macrophages that had phagocytosed R5 or R10 bacteria was followed for up to 18 days by endotoxin measurements (Limulus assay) and immunostaining, with monoclonal antibodies to various parts of the LPS molecule being used. Only 0.1% or less of the macrophageassociated bacteria remained alive after 48 h of incubation, and none were alive on day 7. Although immunostaining showed that LPS was present in both the Lps d and Lps n macrophages during the whole incubation period of 18 days, endotoxin activity in the Lps d macrophages on day 7 was lower than that in the Lps n macrophages, indicating that qualitative modifications of the chemical composition or physical state of the LPS molecule occurred. The interleukin-6 response in the Ity s Lps d macrophages was delayed and of shorter duration compared with that in the Ity s Lps n macrophages. The results suggest that the difference between the LPS-hyporesponsive and-responsive Ity s mice in susceptibility to infection with the R5 mutant was due to the lower activation state of the Lps d macrophages during infection, leading to a lower intracellular killing rate and a lower interleukin-6 response. Deep rough mutant R10 was highly sensitive to the intracellular bactericidal systems of the macrophages. A rapid killing of the bacterium should restrict the infection and may partly compensate for a diminished inflammatory response. The persistence of LPS within the cells is discussed.

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