Streptococcal co-infection augments Candida pathogenicity by amplifying the mucosal inflammatory response.

Streptococcal co-infection augments Candida pathogenicity by amplifying the mucosal inflammatory response.
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DOI:
10.1111/cmi.12216
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发表时间:
2014-02
影响因子:
3.4
通讯作者:
Dongari-Bagtzoglou A
Dongari-Bagtzoglou A
中科院分区:
生物学2区
文献类型:
--
作者:
Xu H;Sobue T;Thompson A;Xie Z;Poon K;Ricker A;Cervantes J;Diaz PI;Dongari-Bagtzoglou A

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缓和组链球菌是普遍存在的口腔病原体,可以促进多细菌生物膜的毒力。使用一种新的小鼠口腔粘膜共感染模型,我们试图首次确定这些生物体是否促进口咽感染中白色念珠菌粘膜生物膜的毒力,并探索致病协同作用的机制。我们发现口腔链球菌在口腔和胃肠道的定植在白色念珠菌的存在下增强。口腔链球菌和白色念珠菌的共同感染显着增加的频率和大小的口腔鹅口疮病变。重要的是,口腔链球菌促进了白色念珠菌的深部器官播散。全小鼠基因组舌微阵列分析表明,当与感染一种生物体的动物相比时,双重感染的动物在嗜酸性反应/趋化性/炎症的主要类别中的基因显著上调,表明炎症反应过度。这种反应依赖于TLR 2信号,因为口腔病变、促炎基因转录和中性粒细胞浸润在TLR 2 −/−动物中减弱。此外,口腔链球菌在体外以TLR 2依赖的方式激活中性粒细胞。总之,本研究确定了口腔念珠菌和白色念珠菌之间以前未被认识到的致病协同作用。这是第一次报告的能力,粘膜真菌细菌修改的毒力的机会真菌病原体。
Mitis-group streptococci are ubiquitous oral commensals that can promote polybacterial biofilm virulence. Using a novel murine oral mucosal co-infection model we sought to determine for the first time whether these organisms promote the virulence of C. albicans mucosal biofilms in oropharyngeal infection and explored mechanisms of pathogenic synergy. We found that Streptococcus oralis colonization of the oral and gastrointestinal tract was augmented in the presence of C. albicans. S. oralis and C. albicans co-infection significantly augmented the frequency and size of oral thrush lesions. Importantly, S. oralis promoted deep organ dissemination of C. albicans. Whole mouse genome tongue microarray analysis showed that when compared with animals infected with one organism, the doubly infected animals had genes in the major categories of neutrophilic response/chemotaxis/inflammation significantly upregulated, indicative of an exaggerated inflammatory response. This response was dependent on TLR2 signalling since oral lesions, transcription of pro-inflammatory genes and neutrophil infiltration, were attenuated in TLR2−/− animals. Furthermore, S. oralis activated neutrophils in a TLR2-dependent manner in vitro. In summary, this study identifies a previously unrecognized pathogenic synergy between oral commensal bacteriaand C. albicans. This is the first report of the ability of mucosal commensal bacteria to modify the virulence of an opportunistic fungal pathogen.
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