Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40.

Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40.
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DOI:
10.1128/spectrum.00106-22
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发表时间:
2022-04-27
影响因子:
3.7
通讯作者:
--
中科院分区:
生物学1区
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--
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许多细菌和真菌病原体通过粘膜表面引起疾病,并在较小程度上通过皮肤表面引起疾病。可能导致阴道上皮细胞疾病的病原体包括金黄色葡萄球菌、A 组和 B 组链球菌、大肠杆菌、淋病奈瑟菌和白色念珠菌。我们之前已经证明,通过使用 CRISPR cas9 敲除突变体和互补的上皮细胞系,葡萄球菌和链球菌超抗原通过免疫共刺激分子 CD40 诱导阴道上皮细胞产生炎症趋化因子。在这项研究中,我们发现潜在的阴道病原体金黄色葡萄球菌、A 族和 B 族链球菌、大肠杆菌、粪肠球菌菌株和白色念珠菌在一定程度上利用 CD40 刺激人阴道上皮细胞产生白细胞介素 8 (IL-8)。相比之下,淋病奈瑟菌似乎并不使用 CD40 来发出 IL-8 产生的信号。正常菌群卷曲乳杆菌和产生罗伊环素的粪肠球菌菌株不诱导 IL-8。这些数据表明,许多潜在的病原体(但没有正常的共生体)诱导IL-8通过CD40帮助破坏人类阴道上皮屏障,从而为药物开发提供潜在的治疗靶点。重要性 大多数细菌和真菌病原体在上皮细胞诱导趋化因子的帮助下引起跨粘膜疾病,并在较小程度上跨皮肤屏障引起疾病。在这项研究中,我们发现潜在的阴道病原体金黄色葡萄球菌、A 组和 B 组链球菌、一些粪肠球菌菌株、大肠杆菌和白色念珠菌使用免疫共刺激分子 CD40 诱导趋化因子白细胞介素 8 的产生。相比之下,淋病奈瑟菌不使用 CD40 来刺激白细胞介素 8。正常的乳杆菌菌群和至少一种粪肠球菌菌株不诱导白介素-8。
Many bacterial and fungal pathogens cause disease across mucosal surfaces, and to a lesser extent through skin surfaces. Pathogens that potentially cause disease vaginally across epithelial cells include Staphylococcus aureus, group A and B streptococci, Escherichia coli, Neisseria gonorrhoeae, and Candida albicans. We have previously shown that staphylococcal and streptococcal superantigens induce inflammatory chemokines from vaginal epithelial cells through the immune costimulatory molecule CD40 through use of a CRISPR cas9 knockout mutant and complemented epithelial cell line. In this study, we show that the potential vaginal pathogens S. aureus, group A and B streptococci, E. coli, an Enterococcus faecalis strain, and C. albicans in part use CD40 to stimulate interleukin-8 (IL-8) production from human vaginal epithelial cells. In contrast, N. gonorrhoeae does not appear to use CD40 to signal IL-8 production. Normal flora Lactobacillus crispatus and an Enterococcus faecalis strain that produces reutericyclin do not induce IL-8. These data indicate that many potential pathogens, but no normal commensals, induce IL-8 to help disrupt the human vaginal epithelial barrier through CD40, thus providing a potential therapeutic target for drug development. IMPORTANCE Most bacterial and fungal pathogens cause disease across mucosal, and to a lesser extent, skin barriers with the help of induced chemokines from epithelial cells. In this study, we showed that potential vaginal pathogens Staphylococcus aureus, group A and B streptococci, some Enterococcus faecalis strains, Escherichia coli, and Candida albicans use the immune costimulatory molecule CD40 to induce the chemokine interleukin-8 production. In contrast, Neisseria gonorrhoeae does not use CD40 to stimulate interleukin-8. Normal flora lactobacilli and at least one E. faecalis strain do not induce interleukin-8.
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期刊: Journal of immunology (Baltimore, Md. : 1950)
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