Murine candidiasis: Sex differences in the severity of tissue lesions are not associated with levels of serum C3 and C5

Ashman, R. B.; Kay, Peter; Lynch, D. M.; Papadimitriou, J. M.

doi:10.1038/icb.1991.2

Cited by 17 publications

(7 citation statements)

References 18 publications

(23 reference statements)

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“…The effect of gender on the ability of a host to resist infectious challenge with C. albicans has been noted previously, with male mice of different inbred strains tending to be more susceptible to infection, even among C5-sufficient strains, where serum C5 concentrations are higher in males than in females. 42,43 This gender specificity appears to be much stronger in BcA72 than in the A/J and B6 controls. Among the C5-sufficient strains, BcA67 displayed a marginally enhanced susceptibility, compared to the B6 controls.…”

Section: Discussionmentioning

confidence: 93%

Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

et al. 2005

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The importance of host factors in determining susceptibility to systemic Candida albicans infections is evident in both humans and mice. We have used a mouse model to study the genetic basis of susceptibility, using the inbred strains A/J and C57BL/6J, which are susceptible and resistant, respectively, based on different parameters of the response to infection. To identify genes responsible for this differential host response, brain and kidney fungal load were measured in 128 [A/J Â C57BL/6J] F 2 mice 48 h after infection with 5 Â 10 4 C. albicans blastospores. Segregation analysis in this informative population identified complement component 5 (C5/Hc) as the major gene responsible for this differential susceptibility (LOD of 22.7 for kidney, 19.0 for brain), with a naturally occurring mutation that causes C5 deficiency leading to enhanced susceptibility. C5 was also found to control heart fungal load, survival time, and serum TNF-a levels during infection. Investigation of the response to C. albicans challenge in a series of AcB/BcA recombinant congenic strains validated the importance of C5 in determining the host response. However, the strains BcA67 and BcA72 showed discordant phenotypes with respect to their C5 status, suggesting additional complexity in the genetic control of the inter-strain difference in susceptibility observed in A/J and C57BL/6J following systemic infection with C. albicans. Genes and Immunity (2005) 6, 672-682.

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Section: Discussionmentioning

confidence: 93%

Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

et al. 2005

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“…Although this deficiency has been eliminated as a factor associated with their increased susceptibility to acute i.v. challenge (Sawyer, 1990;Ashman et al, 1991), it may still play a role during mucosal infections.…”

Section: Antibody Response To C Albicans Mg3mentioning

confidence: 99%

Evaluation of the intranasal challenge route in mice as a mucosal model for Candida albicans infection

et al. 1998

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The intranasal route was used to study Candida albicans infections in mice.Mice from two different inbred strains were challenged intranasally with C.albicans and the level of local and systemic colonization was monitored. DBA/2 mice were highly susceptible to challenge and viable C. albicans disseminated from the lungs to deeper tissues, including kidneys, liver and spleen within 48 h. In contrast, in BALB/c mice challenged in the same manner, C. albicans were retained within the lungs and cleared. Local and systemic anti-C. albicans immune responses were investigated. BALB/c mice exhibited higher titres of serum and mucosal anti-C. albicans IgA than DBN2 mice. Splenocytes from BALB/c mice, but not from DBA/2 mice, produced detectable levels of interleukin-4 and -5 following stimulation with C. albicans antigens. Both DBAI2-and BALB/c-derived splenocytes produced interferon-y and interleukin-10 in response to similar stimulation. In conclusion, the intranasal route provided a simple, non-invasive murine model for investigating C. albicans infection through mucosal surfaces.

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“…1, Supplemental Fig. 1), with a noticeable gender bias, where male mice showed increased susceptibility compared with females (54)(55)(56). Subsequent linkage mapping in [C57BL/6JxSM/J]F2 progeny mapped a novel locus on distal chromosome 15 that we term Carg5 (cumulative peak LOD of 6.09; Fig.…”

Section: Discussionmentioning

confidence: 99%

Genetic Control of Susceptibility to Candida albicans in SM/J Mice

Radovanovic

Leung

Iliescu

et al. 2014

The Journal of Immunology

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In the immunocompromised host, invasive infection with the fungal pathogen Candida albicans is associated with high morbidity and mortality. Sporadic cases in otherwise normal individuals are rare, and they are thought to be associated with genetic predisposition. Using a mouse model of systemic infection with C. albicans, we identified the SM/J mouse strain as unusually susceptible to infection. Genetic linkage studies in informative [C57BL/6JxSM/J]F2 mice identified a major locus on distal chromosome 15, given the appellation Carg5, that regulates C. albicans replication in SM/J mice. Cellular and molecular immunophenotyping experiments, as well as functional studies in purified cell populations from SM/J and C57BL/6J, and in [C57BL/6JxSM/J]F2 mice fixed for homozygous or heterozygous Carg5 alleles, indicate that Carg5-regulated susceptibility in SM/J is associated with a complex defect in the myeloid compartment of these mice. SM/J neutrophils express lower levels of Ly6G, and importantly, they show significantly reduced production of reactive oxygen species in response to stimulation with fMLF and PMA. Likewise, CD11b+Ly6G−Ly6Chi inflammatory monocytes were present at lower levels in the blood of infected SM/J, recruited less efficiently at the site of infection, and displayed blunted oxidative burst. Studies in F2 mice establish strong correlations between Carg5 alleles, Ly6G expression, production of serum CCL2 (MCP-1), and susceptibility to C. albicans. Genomic DNA sequencing of chromatin immunoprecipitated for myeloid proinflammatory transcription factors IRF1, IRF8, STAT1 and NF-κB, as well as RNA sequencing, were used to develop a “myeloid inflammatory score” and systematically analyze and prioritize potential candidate genes in the Carg5 interval.

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Murine candidiasis: Sex differences in the severity of tissue lesions are not associated with levels of serum C3 and C5

Cited by 17 publications

References 18 publications

Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

Genetic control of suceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice

Evaluation of the intranasal challenge route in mice as a mucosal model for Candida albicans infection

Genetic Control of Susceptibility to Candida albicans in SM/J Mice

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