title: Genetic control of natural resistance in mouse macrophages regulating intracellular Legionella pneumophila multiplication in vitro.
abstract: It is known that Legionella pneumophila proliferates in peritoneal macrophage cultures derived from A/J mice but not in macrophage cultures derived from many other strains, including C57BL/6 mice. To analyze the genetic control of this trait and the location of the Legionella resistance-susceptibility gene, we prepared segregating progeny of A/J and C57BL/6 mice and determined the levels of susceptibility of individual mice. Peritoneal macrophages were collected by injecting thioglycolate medium, and macrophage monolayers were infected in vitro with L. pneumophila Philadelphia-1. Counting of colonies on buffered charcoal yeast extract agar plates and Gimenez staining of macrophage monolayers were carried out daily. There was a 10-fold increase in bacterial burden 1 day after infection and a 100-fold increase after 2 days in A/J (susceptible) macrophages. The increase in bacterial burden was always less than 10-fold in macrophages from C57BL/6 (resistant) progenitors, A/J x C57BL/6 F1 hybrids, and C57BL/6 x F1 backcross progeny. The ratios of resistant individuals to susceptible individuals were 22:6 for F2 progeny and 20:22 for A/J x F1 backcross progeny. The fact that the organism did not proliferate in macrophages from B10.A mice demonstrated that major histocompatibility antigens did not regulate the macrophage resistance of C57BL/6-derived mice. The sex and coat color genes of mice were not linked to the resistance-susceptibility gene. We suggest that resistance and susceptibility are controlled by a single gene or closely linked genes which are autosomal and that the resistance allele is dominant. The results of a comparison of the strain distribution pattern of this trait with the distribution pattern of 185 allelic markers in A/J x C57BL/6 and C57BL/6 x A/J recombinant inbred strains suggest that this susceptibility-resistance gene is located in the proximal part of chromosome 15.
authors.affiliation: Department of Microbiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.forename: Y
authors.initials: Y
authors.lastname: Mizuguchi
authors.forename: K
authors.initials: K
authors.lastname: Nomoto
authors.forename: E
authors.initials: E
authors.lastname: Skamene
mesh_terms: D000483:Alleles; D000818:Animals; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D066298:In Vitro Techniques; D007875:Legionella / Q000254:growth & development*; D007876:Legionellosis / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity