Genetic Evidence for the Role of theLvLocus 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.