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 ar e nearly congenic for the Lv locus. Fourteen days after intraperitoneal inf ection, B6 mice had nearly 100-fold more Coccidioides immitis in their lung s than did B10 mice (log 6.2 vs. log 4.8). Furthermore, the time to 50% dea ths was 15 days for B6 and 22 days for B10. Nevertheless, 90% of B10 mice h ad died by day 28, In other mouse strains, we found a direct correlation be tween 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 hig her levels of IL-4 mRNA than did B6 mice, despite having less C, immitis. I n the absence of IL-10, B10 mice are resistant to lethal infection. These r esults suggest that a locus near Lv is responsible for early resistance to coccidioidomycosis but not for modulating the IL-10 and IL-4 responses. Thi s locus is not sufficient to make C57BL mice resistant to coccidioidomycosi s.