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The skin microbiome of caspase-14-deficient mice shows mild dysbiosis
Malgorzata Kubica1, Falk Hildebrand, Brigitta M Brinkman
1Inflammation Research Center, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Abstract:
Caspase-14, an important proteinase involved in filaggrin catabolism, is mainly active in terminally differentiating keratinocytes, where it is required for the generation of skin natural moisturizing factors (NMFs). Consequently, caspase-14 deficient epidermis is characterized by reduced levels of NMFs such as urocanic acid and 2-pyrrolidone-5-carboxylic acid. Patients suffering from filaggrin deficiency are prone to develop atopic dermatitis, which is accompanied with increased microbial burden. Among several reasons, this effect could be due to a decrease in filaggrin breakdown products. In this study, we found that caspase-14(-/-) mice show enhanced antibacterial response compared to wild-type mice when challenged with bacteria. Therefore, we compared the microbial communities between wild-type and caspase-14(-/-) mice by sequencing of bacterial 16S ribosomal RNA genes. We observed that caspase-14 ablation leads to an increase in bacterial richness and diversity during steady-state conditions. Although both wild-type and caspase-14(-/-) skin were dominated by the Firmicutes phylum, the Staphylococcaceae family was reduced in caspase-14(-/-) mice. Altogether, our data demonstrated that caspase-14 deficiency causes the imbalance of the skin-resident bacterial communities.
Insights
Caspase-14 deficiency in mice alters skin bacteria, increasing microbial diversity and richness. This suggests a role for caspase-14 in maintaining a balanced skin microbiome, potentially impacting skin health and conditions like atopic dermatitis.
Area of Science:
- Dermatology
- Microbiology
- Biochemistry
Background:
- Caspase-14 is crucial for filaggrin breakdown and natural moisturizing factor (NMF) generation in skin keratinocytes.
- Reduced NMFs, seen in caspase-14 deficiency, are linked to filaggrin deficiency disorders like atopic dermatitis and increased microbial load.
- Filaggrin breakdown products may influence skin's antibacterial defenses.
Purpose of the Study:
- To investigate the impact of caspase-14 deficiency on the skin microbiome.
- To compare the antibacterial response and microbial community composition between wild-type and caspase-14 knockout mice.
Main Methods:
- Caspase-14 deficient (caspase-14(-/-)) and wild-type mice were challenged with bacteria.
- Bacterial 16S ribosomal RNA gene sequencing was used to analyze skin microbial communities.
- Skin microbial richness and diversity were assessed under steady-state conditions.
Main Results:
- Caspase-14(-/-) mice exhibited an enhanced antibacterial response compared to wild-type controls.
- Caspase-14 ablation resulted in increased bacterial richness and diversity on the skin.
- While both groups were dominated by Firmicutes, the Staphylococcaceae family was reduced in caspase-14(-/-) mice.
Conclusions:
- Caspase-14 deficiency leads to an imbalance in the skin-resident bacterial communities.
- The findings suggest caspase-14 plays a role in regulating the skin microbiome composition.
- Altered skin microbiome due to caspase-14 deficiency may have implications for skin barrier function and susceptibility to infections.
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