Staphylococcus aureus Esx Factors Control Human Dendritic Cell Functions Conditioning Th1/Th17 Response.
Staphylococcus aureus Esx Factors Control Human Dendritic Cell Functions Conditioning Th1/Th17 Response.
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DOI：
10.3389/fcimb.2017.00330
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发表时间：
2017
影响因子：
5.7
通讯作者：
Coccia EM
中科院分区：
文献类型：
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作者：
Cruciani M;Etna MP;Camilli R;Giacomini E;Percario ZA;Severa M;Sandini S;Rizzo F;Brandi V;Balsamo G;Polticelli F;Affabris E;Pantosti A;Bagnoli F;Coccia EM
条件致病菌金黄色葡萄球菌（S.金黄色葡萄球菌）是医院和社区获得性感染的主要原因。此外，世界范围内出现了许多耐药菌株，因此，迫切需要确定新的治疗和预防策略。在本研究中，我们描述了感染大流行耐甲氧西林USA 300 S的影响。金黄色葡萄球菌菌株对人原代树突状细胞（DC）的作用，树突状细胞是免疫应答的关键启动子和调节子。特别是，在葡萄球菌毒力因子中，在人DC环境中研究了由VII型样分泌系统Ess（ESAT-6样分泌系统）分泌的两种小的酸性二聚体蛋白EsxA和EsxB的功能。通过使用野生型（wt）USA 300和携带esxA（ΔesxA）、esxB（ΔesxB）或两种基因缺失（ΔesxAB）的三种同基因突变体进行细菌进入、复制速率以及DC成熟、凋亡、信号通路激活和细胞因子产生的比较分析。色葡萄与wt USA 300、ΔesxAB和ΔesxB菌株相比，仅缺乏EsxA蛋白的金黄色葡萄球菌突变体（ΔesxA）在感染的DC中刺激更强的促凋亡表型。当分析携带esxB缺失的突变体（ΔesxB）时，在感染的DC中发现，相对于用wt对应物和其他esx突变体攻击的那些DC，更高的调节和促炎介质的产生。根据这些数据，与用来自野生型USA 300-、ΔesxAB-和Δ esxA-感染的培养物的上清液调节的那些相比，来自Δ esxB-感染的DC的上清液促进IFN-γ和IL-17从CD 4 + T细胞的更强释放。虽然，S.尽管我们还没有完全了解金黄色葡萄球菌与人DC的关系，但我们的数据表明细胞因子的产生和凋亡过程都受到Esx因子的调节，从而表明这些蛋白在DC介导的对S.金黄色。
The opportunistic pathogen Staphylococcus aureus (S. aureus) is a major cause of nosocomial- and community-acquired infections. In addition, many antibiotic-resistant strains are emerging worldwide, thus, there is an urgent unmet need to pinpoint novel therapeutic and prophylactic strategies. In the present study, we characterized the impact of infection with the pandemic methicillin-resistant USA300 S. aureus strain on human primary dendritic cells (DC), key initiators and regulators of immune responses. In particular, among staphylococcal virulence factors, the function of EsxA and EsxB, two small acidic dimeric proteins secreted by the type VII-like secretion system Ess (ESAT-6-like secretion system), was investigated in human DC setting. A comparative analysis of bacterial entry, replication rate as well as DC maturation, apoptosis, signaling pathway activation and cytokine production was performed by using wild type (wt) USA300 and three isogenic mutants carrying the deletion of esxA (ΔesxA), esxB (ΔesxB), or both genes (ΔesxAB). The S. aureus mutant lacking only the EsxA protein (ΔesxA) stimulated a stronger pro-apoptotic phenotype in infected DC as compared to wt USA300, ΔesxAB, and ΔesxB strains. When the mutant carrying the esxB deletion (ΔesxB) was analyzed, a higher production of both regulatory and pro-inflammatory mediators was found in the infected DC with respect to those challenged with the wt counterpart and the other esx mutants. In accordance with these data, supernatant derived from ΔesxB-infected DC promoted a stronger release of both IFN-γ and IL-17 from CD4+ T cells as compared with those conditioned with supernatants derived from wild type USA300-, ΔesxAB-, and ΔesxA-infected cultures. Although, the interaction of S. aureus with human DC is not yet fully understood, our data suggest that both cytokine production and apoptotic process are modulated by Esx factors, thus indicating a possible role of these proteins in the modulation of DC-mediated immunity to S. aureus.