The p47 GTPases Igtp and Irgb10 Map to the Chlamydia Trachomatis Susceptibility Locus Ctrq-3 and Mediate Cellular Resistance in Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 38; pp. 14092 - 14097
• Main Authors: Bernstein-Hanley, Isaac, Coers, Jörn, Balsara, Zarine R., Taylor, Gregory A., Starnbach, Michael N., Dietrich, William F.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 19.09.2006; National Acad Sciences
• Subjects: Amino Acid Sequence; Animals; Biological Sciences; Cells, Cultured; Chlamydia; Chlamydia Infections - genetics; Chlamydia Infections - immunology; Chlamydia trachomatis; Chlamydia trachomatis - immunology; Chromosome Mapping; Chromosomes; Chromosomes, Mammalian; Disease Susceptibility; DNA; Fibroblasts; Fibroblasts - cytology; Fibroblasts - physiology; Genetics; Genomics; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Humans; Immunity (Disease); Infections; Interferon; Interferon-gamma - metabolism; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Models, Genetic; Molecular Sequence Data; Pathogens; Phenotypes; Quantitative trait loci; Rodents
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0603338103

Infections caused by the bacteria Chlamydia trachomatis contribute to diverse pathologies in a variety of human populations. We previously used a systemic model of C trachomatis infection in mice to map three quantitative trait loci that influence in vivo susceptibility differences between the C57BL/6J and C3H/HeJ inbred strains of mouse. One of these quantitative trait loci, Ctrq-3, influences an IFN-γ-dependent susceptibility difference in primary embryonic fibroblasts isolated from these strains. Here we use fine structure mapping in congenic fibroblasts carrying DNA from the susceptible parent to localize the effect of Ctrq-3 to a 1.2-megabase interval of genomic DNA that contains Irgb10 and Igtp, two members of the IFN-γ-inducible p47 family of GTPases. This class of proteins has been widely implicated in resistance to intracellular pathogens in mice. We analyzed expression of Irgb10 and Igtp in parental and congenic embryonic fibroblasts treated with IFN-γ and found that relatively resistant fibroblasts express more Irgb10 than relatively susceptible fibroblasts. However, we also found that abolishing the expression of either Irgb10 or Igtp increases susceptibility of embryonic fibroblasts to C. trachomatis. Thus, we conclude that, although a difference in Irgb10 expression is likely responsible for the effect of Ctrq-3 on susceptibility to C. trachomatis, both genes play a role in intracellular resistance to C. trachomatis.