Abstract:
:Genetic factors that regulate the pathogenesis of pneumonia caused by the fungus Cryptococcus neoformans are 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. neoformans ATCC 24067. The aim of the present study was to characterize the inflammatory response of C3H/HeN mice following C. neoformans pulmonary 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 Cnes4 and a susceptibility allele at Cnes5. These studies reveal additional genetic complexity of the host response to C. neoformans that is associated with divergent patterns of pulmonary inflammation.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Carroll SF,Lafferty EI,Flaczyk A,Fujiwara TM,Homer R,Morgan K,Loredo-Osti JC,Qureshi STdoi
10.1128/IAI.00417-12subject
Has Abstractpub_date
2012-12-01 00:00:00pages
4167-76issue
12eissn
0019-9567issn
1098-5522pii
IAI.00417-12journal_volume
80pub_type
杂志文章abstract::We compared the immune defense of mice with chronic granulomatous disease (CGD mice) with that of wild-type C57BL/6 mice for their response to Sporothrix schenckii. A subcutaneous injection of 5 x 10(4) CFU S. schenckii strain IFM41598 into CGD mice resulted in systemic infection and death within 84 days. In contrast,...
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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