Genetic evidence for the role of the Lv locus in early susceptibility but not IL-10 synthesis in experimental coccidioidomycosis in C57BL mice.
Loci on chromosome 4 near Lv and on chromosome 6 near Tnfr1 are associated with resistance to coccidioidomycosis in mice. To assess the importance of the Lv locus, we compared C57BL/6 (B6) with C57BL/10 (B10), strains that are nearly congenic for the Lv locus. Fourteen days after intraperitoneal infection, B6 mice had nearly 100-fold more Coccidioides immitis in their lungs than did B10 mice (log 6.2 vs. log 4.8). Furthermore, the time to 50% deaths was 15 days for B6 and 22 days for B10. Nevertheless, 90% of B10 mice had died by day 28. In other mouse strains, we found a direct correlation between lung colony-forming units and levels of interleukin (IL)-10 and IL-4 mRNA, but B10 mice had 100-fold higher lung levels of IL-10 and 10-fold higher levels of IL-4 mRNA than did B6 mice, despite having less C. immitis. In the absence of IL-10, B10 mice are resistant to lethal infection. These results suggest that a locus near Lv is responsible for early resistance to coccidioidomycosis but not for modulating the IL-10 and IL-4 responses. This locus is not sufficient to make C57BL mice resistant to coccidioidomycosis.
Fierer
J
J
Departments of Medicine, VA San Diego Healthcare System and University of California, San Diego, School of Medicine, San Diego, CA 92161, USA. jfierer@ucsd.edu
Walls
L
L
Kirkland
T N
TN
D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D003045:Coccidioides / Q000302:isolation & purification*; D003047:Coccidioidomycosis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D005260:Female; D020022:Genetic Predisposition to Disease; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics
D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10; D015847:Interleukin-4