A Bacterial Epigenetic Switch in Non-typeable Haemophilus influenzae Modifies Host Immune Response During Otitis Media.
A Bacterial Epigenetic Switch in Non-typeable Haemophilus influenzae Modifies Host Immune Response During Otitis Media.
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DOI：
10.3389/fcimb.2020.512743
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发表时间：
2020
影响因子：
5.7
通讯作者：
Brockman KL
中科院分区：
文献类型：
--
作者：
Robledo-Avila FH;Ruiz-Rosado JD;Partida-Sanchez S;Brockman KL
不可分型的流感嗜血杆菌（NTHi）引起人类气道的多种疾病，是急性中耳炎和治疗失败的中耳炎的主要细菌病原体。NTHi利用阶段可变表观遗传调控系统，称为阶段变异，以促进在人类宿主的多个位点内的适应和生存。NTHi相位变化影响许多疾病相关表型，如生物膜形成、抗生素耐药性和调理。我们之前已经确定了一个有利的选择，为特定的相位变化状态，这显著影响实验性中耳炎的严重程度和慢性。在这项研究中，我们利用了NTHi变体的纯培养物，其中modA被锁定在ON或OFF状态，因此modA无法发生相位变化。这些锁定变异被用来评估实验性中耳炎的进展，并定义每个亚群诱导的特异性免疫反应。虽然每个亚群引起的初始疾病是相似的，但每个亚群引起的免疫反应是独特的。在疾病期间，modA2 OFF变异在体外和中耳内诱导巨噬细胞显著增强活化。相反，modA2 ON变体诱导了更大的中性粒细胞胞外陷阱反应，这导致了modA2 ON变体更大的杀伤。这些数据表明，NTHi阶段的变化不仅促进了适应，而且还允许细菌在疾病期间改变免疫反应。了解这些复杂的细菌-宿主相互作用和细菌因子的调控对开发更好的诊断、治疗和预防这些细菌病原体的策略至关重要。
Non-typeable Haemophilus influenzae (NTHi) causes multiple diseases of the human airway and is a predominant bacterial pathogen of acute otitis media and otitis media in which treatment fails. NTHi utilizes a system of phase variable epigenetic regulation, termed the phasevarion, to facilitate adaptation and survival within multiple sites of the human host. The NTHi phasevarion influences numerous disease-relevant phenotypes such as biofilm formation, antibiotic resistance, and opsonization. We have previously identified an advantageous selection for a specific phasevarion status, which significantly affects severity and chronicity of experimental otitis media. In this study, we utilized pure cultures of NTHi variants in which modA was either locked ON or locked OFF, and thus modA was unable to phase vary. These locked variants were used to assess the progression of experimental otitis media and define the specific immune response induced by each subpopulation. Although the initial disease caused by each subpopulation was similar, the immune response elicited by each subpopulation was unique. The modA2 OFF variant induced significantly greater activation of macrophages both in vitro and within the middle ear during disease. In contrast, the modA2 ON variant induced a greater neutrophil extracellular trap response, which led to greater killing of the modA2 ON variant. These data suggest that not only does the NTHi phasevarion facilitate adaptation, but also allows the bacteria to alter immune responses during disease. Understanding these complex bacterial-host interactions and the regulation of bacterial factors responsible is critical to the development of better diagnostic, treatment, and preventative strategies for these bacterial pathogens.
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影响因子：
5.3
作者：
Hong, Wenzhou;Juneau, Richard A.;Swords, W. Edward
通讯作者：
Swords, W. Edward
影响因子：
4.2
作者：
Gauntlett, Jonathan C.;Nilsson, Hans-Olof;Benghezal, Mohammed
通讯作者：
Benghezal, Mohammed
影响因子：
4.3
作者：
Hood D;Moxon R;Purnell T;Richter C;Williams D;Azar A;Crompton M;Wells S;Fray M;Brown SD;Cheeseman MT
通讯作者：
Cheeseman MT
影响因子：
8
作者：
Goodman, S. D.;Obergfell, K. P.;Bakaletz, L. O.
通讯作者：
Bakaletz, L. O.
DOI：
10.1073/pnas.1802261115
发表时间：
2018-07-24
影响因子：
11.1
作者：
Li, Wenchao;Zhang, Xinyun;Shen, Hao
通讯作者：
Shen, Hao