Antimicrobial peptide-producing dermal preadipocytes defend against Candida albicans skin infection via the FGFR-MEK-ERK pathway.
Antimicrobial peptide-producing dermal preadipocytes defend against Candida albicans skin infection via the FGFR-MEK-ERK pathway.
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DOI：
10.1371/journal.ppat.1011754
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发表时间：
2023-11
期刊：
影响因子：
6.7
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中科院分区：
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真皮成纤维细胞（dFB）通过分化成产生抗菌肽凯萨林菌素的前脂肪细胞（pAds）来防御深部细菌皮肤感染;这种分化被称为真皮反应性脂肪生成反应。然而，dFB在真菌感染中的作用仍然未知。在这里，我们发现，cathelicidin生产pAds在皮肤念珠菌肉芽肿患者的皮肤病变中大量存在。其次，我们发现皮肤白色念珠菌（C。白色念珠菌感染小鼠后，皮肤脂肪生成反应明显增强，并诱导cathelicidin表达，而过氧化物酶体增殖物激活受体γ（PPAR γ）抑制剂抑制脂肪生成可降低皮肤对白色念珠菌的抵抗力。白色念珠菌。在离体条件下，C. pAds中cathelicidin的表达受白色念珠菌分泌物的诱导，而分化的pAds明显抑制了白色念珠菌的生长。白色念珠菌产生cathelicidin。最后，我们证明了C.白色念珠菌通过FGFR-MEK-ERK途径诱导pAd中的抗微生物应答。总之，我们的数据揭示了dFB在防御由C引起的皮肤感染中以前未知的作用。白色念珠菌白色念珠菌（C.白色念珠菌）是最常引起人类真菌感染的病原体。它通常栖息于几乎30 - 70%健康个体的皮肤表面、生殖器和/或肠粘膜。在某些情况下，如皮肤屏障完整性受损或免疫抑制，C.白色念珠菌可引起粘膜和皮肤念珠菌病。在这里，我们证明了皮肤成纤维细胞对C。白色念珠菌皮肤感染，这是以前未知的。首先，我们发现在感染C.的人类和小鼠皮肤病变中，产生凯萨林菌素的前脂肪细胞（pAds）数量增加。albicans，表明C.白色念珠菌感染触发皮肤反应性脂肪生成反应。此外，我们发现通过给予过氧化物酶体增殖物激活受体γ的药理学抑制剂来抑制脂肪形成，或抑制cathelicidin表达，削弱了皮肤对C.白色念珠菌最后，我们表明pAds响应C.通过FGFR-MEK-ERK途径产生凯萨林菌素。白色念珠菌感染我们的研究结果可能为深部皮肤念珠菌病的治疗提供新的治疗策略。
Dermal fibroblasts (dFBs) defend against deep bacterial skin infections by differentiating into preadipocytes (pAds) that produce the antimicrobial peptide cathelicidin; this differentiation is known as the dermal reactive adipogenesis response. However, the role of dFBs in fungal infection remains unknown. Here, we found that cathelicidin-producing pAds were present in high numbers in skin lesions from patients with cutaneous Candida granulomas. Second, we showed that dermal Candida albicans (C. albicans) infection in mice robustly triggered the dermal reactive adipogenesis response and induced cathelicidin expression, and inhibition of adipogenesis with pharmacological inhibitors of peroxisome proliferator–activated receptor γ (PPARγ) impaired skin resistance to C. albicans. In vitro, C. albicans products induced cathelicidin expression in pAds, and differentiating pAds markedly suppressed the growth of C. albicans by producing cathelicidin. Finally, we showed that C. albicans induced an antimicrobial response in pAds through the FGFR-MEK-ERK pathway. Together, our data reveal a previously unknown role of dFBs in the defense against skin infection caused by C. albicans. Candida albicans (C. albicans) is the pathogen that most commonly causes human fungal infections. It normally inhabits the skin surface, genital and/or intestinal mucosa of almost 30–70% healthy individuals. In certain instances, such as impairment of skin barrier integrity or immunosuppression, C. albicans can cause mucosal and cutaneous candidiasis. Here, we demonstrated the protective role of dermal fibroblasts against C. albicans skin infection, which is previously unknown. Firstly, we found that the number of cathelicidin-producing preadipocytes (pAds) increased in both human and mouse skin lesions infected with C. albicans, indicating that C. albicans infection triggers a dermal reactive adipogenesis response. Furthermore, we found inhibiting adipogenesis by administration of pharmacological inhibitors of peroxisome proliferator–activated receptor γ, or suppressing cathelicidin expression, impaired skin resistance to C. albicans. Finally, we showed that pAds produced cathelicidin through the FGFR-MEK-ERK pathway in response to C. albicans infection. Our results could provide new therapeutic strategies for the treatment of deep cutaneous candidiasis.
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影响因子：
3.6
作者：
Driskell RR;Jahoda CA;Chuong CM;Watt FM;Horsley V
通讯作者：
Horsley V
DOI：
10.1126/science.aam9949
发表时间：
2017-08-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Byndloss MX;Olsan EE;Rivera-Chávez F;Tiffany CR;Cevallos SA;Lokken KL;Torres TP;Byndloss AJ;Faber F;Gao Y;Litvak Y;Lopez CA;Xu G;Napoli E;Giulivi C;Tsolis RM;Revzin A;Lebrilla CB;Bäumler AJ
通讯作者：
Bäumler AJ
白色念珠菌的吞噬作用抑制巨噬细胞的自噬流
影响因子：
--
作者：
Duan Z;Chen Q;Du L;Tong J;Xu S;Zeng R;Ma Y;Chen X;Li M
通讯作者：
Li M
影响因子：
2.1
作者：
Bergstrom, Anders;Licht, Tine R.;Bahl, Martin I.
通讯作者：
Bahl, Martin I.
影响因子：
4.9
作者：
Fang, Szu-Yun;Wei, Kai-Che;Sun, Pei-Lun
通讯作者：
Sun, Pei-Lun