Bibliographic Details
| Title: |
Susceptibility to Progressive Cryptococcus neoformansPulmonary Infection Is Regulated by Loci on Mouse Chromosomes 1 and 9 |
| Authors: |
Carroll, Scott F., Lafferty, Erin I., Flaczyk, Adam, Fujiwara, T. Mary, Homer, Robert, Morgan, Kenneth, Loredo-Osti, J C., Qureshi, Salman T. |
| Source: |
Infection and Immunity; October 2012, Vol. 80 Issue: 12 p4167-4176, 10p |
| Abstract: |
ABSTRACTGenetic factors that regulate the pathogenesis of pneumonia caused by the fungus Cryptococcus neoformansare poorly understood. Through a phenotypic strain survey we observed that inbred C3H/HeN mice develop a significantly greater lung fungal burden than mice of the resistant CBA/J strain 4 weeks following intratracheal infection with C. neoformansATCC 24067. The aim of the present study was to characterize the inflammatory response of C3H/HeN mice following C. neoformanspulmonary infection and to identify genetic loci that regulate host defense. Following cryptococcal infection, C3H/HeN mice demonstrated a Th2 immune response with heightened airway and tissue eosinophilia, goblet cell metaplasia, and significantly higher lung interleukin-5 (IL-5) and IL-13 protein expression relative to CBA/J mice. Conversely, CBA/J mice exhibited greater airway and tissue neutrophilia that was associated with significantly higher pulmonary expression of gamma interferon, CXCL10, and IL-17 proteins than C3H/HeN mice. Using the fungal burden at 4 weeks postinfection as a phenotype, genome-wide quantitative trait locus (QTL) analysis among 435 segregating (C3H/HeN × CBA/J)F2 (C3HCBAF2) hybrids identified two significant QTLs on chromosomes 1 (Cnes4) and 9 (Cnes5) that control susceptibility to cryptococcal pneumonia in an additive manner. Susceptible C3H/HeN mice carry a resistance allele at Cnes4and a susceptibility allele at Cnes5. These studies reveal additional genetic complexity of the host response to C. neoformansthat is associated with divergent patterns of pulmonary inflammation. |
| Database: |
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