Phase variable acetylation of lipooligosaccharide modifies antibody production and opsonophagocytic killing of non-typeable Haemophilus influenzae.
Phase variable acetylation of lipooligosaccharide modifies antibody production and opsonophagocytic killing of non-typeable Haemophilus influenzae.
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脂寡糖的相变乙酰化改变了抗体的产生和对非类型流感嗜血杆菌的嗜吞噬细胞杀伤。
DOI：
10.1016/j.isci.2023.107785
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发表时间：
2023-10-20
期刊：
影响因子：
5.8
通讯作者：
Brockman, Kenneth L.
中科院分区：
文献类型：
--
作者：
Wills, Brandon M.;Garai, Preeti;Dickinson, Quinn;Meyer, Jesse G.;Brockman, Kenneth L.
不可分型流感嗜血杆菌（NTHi）每年导致数百万人感染。虽然人们主要知道它会引起中耳炎，但最近的研究表明，NTHi正在成为侵袭性感染的主要病原体，这促使人们需要新的疫苗和治疗方法。低脂寡糖（LOS）由于其免疫原性和外膜定位已被确定为潜在的候选疫苗。然而，参与LOS合成的基因的相位变量表达使疫苗开发变得复杂。在这项研究中，我们使用鼠中耳炎模型来研究oafA（一种参与LOS生物合成的基因）的阶段变化如何影响抗体在感染反应中的产生。我们发现OafA对LOS的乙酰化抑制了感染期间LOS特异性抗体的产生，并且表达乙酰化LOS的NTHi随后更好地保护其免受调理吞噬细胞的杀伤。这些发现强调了理解阶段变量修饰如何影响疫苗效力和成功的重要性。OafA相可变乙酰化NTHi脂质低聚糖乙酰化抑制感染期间抗LOS抗体的产生LOS的乙酰化阻断调理和吞噬杀伤生物化学;免疫学
Non-typeable Haemophilus influenzae (NTHi) causes millions of infections each year. Though it is primarily known to cause otitis media, recent studies have shown NTHi is emerging as a primary pathogen for invasive infection, prompting the need for new vaccines and treatments. Lipooligosaccharide (LOS) has been identified as a potential vaccine candidate due to its immunogenic nature and outer membrane localization. Yet, phase variable expression of genes involved in LOS synthesis has complicated vaccine development. In this study, we used a chinchilla model of otitis media to investigate how phase variation of oafA, a gene involved in LOS biosynthesis, affects antibody production in response to infection. We found that acetylation of LOS by OafA inhibited production of LOS-specific antibodies during infection and that NTHi expressing acetylated LOS were subsequently better protected against opsonophagocytic killing. These findings highlight the importance of understanding how phase variable modifications might affect vaccine efficacy and success. OafA phase variably acetylates NTHi lipooligosaccharide Acetylation inhibits production of anti-LOS antibodies during infection Acetylation of LOS blocks opsonization and phagocytic killing Biological sciences; Biochemistry; Immunology
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嗜血性流感的磷脂改性的脂肪糖抑制ATP诱导的肺上皮细胞释放IL-1β。
DOI：
10.3390/molecules23081979
发表时间：
2018-08-08
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Richter K;Koch C;Perniss A;Wolf PM;Schweda EKH;Wichmann S;Wilker S;Magel I;Sander M;McIntosh JM;Padberg W;Grau V
通讯作者：
Grau V
DOI：
10.3205/cto000114
发表时间：
2014-01-01
期刊：
GMS current topics in otorhinolaryngology, head and neck surgery
影响因子：
--
作者：
Minovi, Amir;Dazert, Stefan
通讯作者：
Dazert, Stefan
影响因子：
3.1
作者：
Phillips, Zachary N.;Brizuela, Charles;Atack, John M.
通讯作者：
Atack, John M.
影响因子：
5.8
作者：
Hong, Wenzhou;Peng, Daxin;Gu, Xin-Xing
通讯作者：
Gu, Xin-Xing
影响因子：
1.7
作者：
Kadowaki, Yoshinori;Hirano, Takashi;Suzuki, Masashi
通讯作者：
Suzuki, Masashi