Cooperation between physiological defenses and immune resistance produces asymptomatic carriage of a lethal bacterial pathogen.
Cooperation between physiological defenses and immune resistance produces asymptomatic carriage of a lethal bacterial pathogen.
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DOI：
10.1126/sciadv.adg8719
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发表时间：
2023-06-23
期刊：
影响因子：
13.6
通讯作者：
Ayres, Janelle S.
中科院分区：
文献类型：
--
作者：
Chen, Grischa Y.;Thorup, Natalia R.;Miller, Abigail J.;Li, Yao-Cheng;Ayres, Janelle S.
动物进化出两种防御策略来抵御感染。拮抗策略包括免疫抗性机制，其作用是杀死入侵的病原体。协同防御或生理防御介导宿主适应感染状态，限制生理损伤和疾病，而不杀死病原体，并且已显示导致致命病原体的无症状携带和传播。在这里，我们证明了生理防御与适应性免疫反应合作，产生长期无症状的致命肠道鼠病原体，啮齿类柠檬酸杆菌。无症状携带遗传毒性C。啮齿类提供了对随后感染的免疫抵抗力。免疫保护依赖于系统性抗体应答和病原体毒力行为，而不是特异性毒力抗原的识别。最后，我们证明了一个无毒的C。啮齿类动物在该领域具有对LPS结构重要的基因的背景突变。我们的工作揭示了无症状感染如何在免疫耐药性的机制上产生，介导排除表型毒性肠道病原体以促进无症状携带。涉及饮食方法和改良病原体的疫苗战略框架。
Animals evolved two defense strategies to survive infections. Antagonistic strategies include immune resistance mechanisms that operate to kill invading pathogens. Cooperative or physiological defenses mediate host adaptation to the infected state, limiting physiological damage and disease, without killing the pathogen, and have been shown to cause asymptomatic carriage and transmission of lethal pathogens. Here, we demonstrate that physiological defenses cooperate with the adaptive immune response to generate long-term asymptomatic carriage of the lethal enteric murine pathogen, Citrobacter rodentium. Asymptomatic carriage of genetically virulent C. rodentium provided immune resistance against subsequent infections. Immune protection was dependent on systemic antibody responses and pathogen virulence behavior rather than the recognition of specific virulent antigens. Last, we demonstrate that an avirulent strain of C. rodentium in the field has background mutations in genes that are important for LPS structure. Our work reveals insight into how asymptomatic infections can arise mechanistically with immune resistance, mediating exclusion of phenotypically virulent enteric pathogen to promote asymptomatic carriage. A framework for vaccine strategy involving dietary approaches and modified pathogens.
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高浓度下的丁酸酯补充剂会改变肠细菌群落，并减少感染了柠檬酸啮齿动物的小鼠的肠道炎症。
影响因子：
4.8
作者：
Jiminez JA;Uwiera TC;Abbott DW;Uwiera RRE;Inglis GD
通讯作者：
Inglis GD
DOI：
10.1038/nri3535
发表时间：
2013-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Ayres JS
通讯作者：
Ayres JS
影响因子：
4.4
作者：
Hawkey J;Hamidian M;Wick RR;Edwards DJ;Billman-Jacobe H;Hall RM;Holt KE
通讯作者：
Holt KE
影响因子：
3.2
作者：
Brockhausen, Inka;Hu, Bo;Feng, Lu
通讯作者：
Feng, Lu