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Publication : Genetic resistance of mice to Mycobacterium paratuberculosis is influenced by Slc11a1 at the early but not at the late stage of infection.

First Author  Roupie V Year  2008
Journal  Infect Immun Volume  76
Issue  5 Pages  2099-105
PubMed ID  18285491 Mgi Jnum  J:134454
Mgi Id  MGI:3788936 Doi  10.1128/IAI.01137-07
Citation  Roupie V, et al. (2008) Genetic resistance of mice to Mycobacterium paratuberculosis is influenced by Slc11a1 at the early but not at the late stage of infection. Infect Immun 76(5):2099-105
abstractText  We have recently described the development of a luminescent Mycobacterium paratuberculosis strain of bovine origin expressing the luxAB genes of Vibrio harveyi. With this luminescent isolate, fastidious and costly enumeration of CFU by plating them on agar can be replaced by easy and rapid luminometry. Here, we have reevaluated the effect of Slc11a1 (formerly Nramp1) polymorphism on susceptibility to M. paratuberculosis, using this luminometric method. A series of inbred mouse strains were infected intravenously with luminescent M. paratuberculosis S-23 and monitored for bacterial replication in spleen, liver, and lungs for 12 weeks. The results indicate that, as for Mycobacterium avium subsp. avium, innate resistance to infection is genetically controlled by Slc11a1. In BALB/c, congenic BALB.B10-H2(b) (BALB/c background; H-2(b)), C57BL/6, and beige C57BL/6(bg/)(bg) mice (all Slc11a1(s)), bacterial numbers in spleen and liver remained unchanged during the first 4 weeks of infection, whereas in DBA/2 and congenic BALB/c.DBA/2 (C.D2) mice (both Slc11a1(r)) and in (C57BL/6 x DBA/2)F(1) mice (Slc11a1(s/r)), the bacterial numbers had decreased more than 10-fold at 4 weeks postinfection in both male and female mice. At later time points, additional differences in bacterial replication were observed between the susceptible mouse strains, particularly in the liver. Whereas bacterial numbers in the liver gradually decreased more than 100-fold in C57BL/6 mice between week 4 and week 12, bacterial numbers were stable in livers from BALB/c and beige C57BL/6(bg/)(bg) mice during this period. Mycobacterium-specific gamma interferon responses developed earlier and to a higher magnitude in C57BL/6 mice than in BALB/c mice and were lowest in resistant C.D2 mice.
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