Mucosal Tolerance to a Bacterial Superantigen Indicates a Novel Pathway To Prevent Toxic Shock

L. Vincent Collins; Kristina Eriksson; Robert G. Ulrich; Andrej Tarkowski

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Mucosal Tolerance to a Bacterial Superantigen Indicates a Novel Pathway To Prevent Toxic Shock

机译：细菌超抗原的粘膜耐受性表明了预防毒性休克的新途径

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Enterotoxins with superantigenic properties secreted during systemic Staphylococcus aureus infection are responsible for toxic shock. We show that intranasal administration of staphylococcal enterotoxin A (SEA), but not a recombinant SEA lacking superantigenic activity, protected mice against lethal systemic SEA challenge. Protection was superantigen specific since intranasal exposure to SEA would not protect against death caused by subsequent toxic shock syndrome toxin 1 systemic challenge. Protection was neither due to selective depletion of SEA-specific T-cell receptor Vβ families nor due to production of neutralizing anti-SEA antibodies. Importantly, the production of interleukin 10 (IL-10) induced by “tolerization” (that is, by the induction of immunological tolerance) contributed to the observed protection against lethal superantigen-triggered disease. In support of this notion we found that (i) significantly increased levels of IL-10 in sera of “tolerized” animals (that is, animals rendered tolerant) and (ii) IL-10?/? mice could not be tolerized by mucosal SEA administration. Altogether, this is the first study to show that mucosal tolerance to a superantigen is readily triggered by means of immunodeviation.

机译：全身性金黄色葡萄球菌感染过程中分泌的具有超抗原特性的肠毒素是引起中毒性休克的原因。我们表明，鼻内注射的葡萄球菌肠毒素A（SEA），而不是缺乏超抗原活性的重组SEA，可以保护小鼠免受致命的系统性SEA攻击。保护是超抗原特异性的，因为鼻内暴露于SEA不能防止随后的毒性休克综合征毒素1全身性攻击引起的死亡。保护既不是由于选择性清除SEA特异性T细胞受体Vβ家族，也不是由于产生中和性抗SEA抗体。重要的是，通过“耐受”（即通过诱导免疫耐受）诱导的白介素10（IL-10）的产生有助于观察到针对致命性超抗原触发疾病的保护。为了支持这一观点，我们发现（i）“耐受的”动物（即具有耐受性的动物）的血清中IL-10的水平显着提高，以及（ii）IL-10 ？/？粘膜SEA给药不能耐受小鼠。总而言之，这是第一项表明超免疫原的粘膜耐受性易于通过免疫偏离触发的研究。 展开▼

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《Infection and immunity》 |2002年第5期|共6页

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L. Vincent Collins; Kristina Eriksson; Robert G. Ulrich; Andrej Tarkowski;
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1. Mucosal Tolerance to a Bacterial Superantigen Indicates a Novel Pathway To Prevent Toxic Shock [J] . L. Vincent Collins, Kristina Eriksson, Robert G. Ulrich, Infection and immunity . 2002,第5期

机译：细菌超抗原的粘膜耐受性表明了预防毒性休克的新途径

2. Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome. [J] . Chau TA, McCully ML, Brintnell W, Nature medicine . 2009,第6期

机译：葡萄球菌细胞壁上的Toll样受体2配体下调超抗原诱导的T细胞活化并预防中毒性休克综合征。

3. Gram-positive bacterial superantigen outside-in signaling causes toxic shock syndrome. (Special Issue: Engineering toxins for 21st century therapies.) [J] . Brosnahan A. J., Schlievert P. M. The FEBS journal . 2011,第23期

机译：革兰氏阳性细菌超抗原由内而外的信号传导引起中毒性休克综合症。（特刊：21世纪疗法的工程毒素。）

4. Involvement of streptococcal superantigens in streptococcal toxic shock syndrome [C] . Lily Yang, Mark Thomas, Andrew Woodhouse, Lancefield International Symposium on Streptococci and Streptococcal Diseases . 2006

机译：链球菌超抗原在链球菌有毒休克综合征中的参与

5. Generation and partial characterization of a regulatory T cell phenotype following repeated in vivo treatment with the staphylococcal superantigen toxic shock syndrome toxin-1. [D] . Cameron, Scott. 2005

机译：葡萄球菌超抗原毒性休克综合征毒素-1反复体内治疗后，调节性T细胞表型的生成和部分表征。

6. Mucosal Tolerance to a Bacterial Superantigen Indicates a Novel Pathway To Prevent Toxic Shock [O] . L. Vincent Collins, Kristina Eriksson, Robert G. Ulrich, 2002

机译：细菌超抗原的粘膜耐受性表明了预防毒性休克的新途径

7. Mucosal Tolerance to a Bacterial Superantigen Indicates a Novel Pathway To Prevent Toxic Shock [O] . Collins, L. Vincent, Eriksson, Kristina, Ulrich, Robert G., 2002

机译：细菌超抗原的粘膜耐受性表明了预防毒性休克的新途径

8. Staphylococcal Enterotoxins, Toxic Shock Syndrome Toxin-I, and Streptococcal Pyrogenic Exotoxins: Some Basic Biology of Bacterial Superantigens [R] . Krakauer, T. , Stiles, B. G. 2003

机译：葡萄球菌肠毒素，毒性休克综合征毒素-I和链球菌热原外毒素：细菌超抗原的一些基本生物学

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2. 中分子羟乙基淀粉对脓毒性休克病人胃粘膜灌注的影响 [J] . 吴建浓 ,雷澍 ,方强 . 江西医药 . 2006,第008期

3. 灵长类动物模型研究表明：无细胞百日咳疫苗不能有效预防百日咳感染和阻断细菌的传播 [J] . 邵祝军 . 中华预防医学杂志 . 2014,第012期

4. 超抗原活化的耐受性淋巴细胞防治高危角膜移植免疫排斥反应的实验研究 [J] . 徐健 ,接英 ,陈钰 . 眼科 . 2009,第005期

5. 多巴胺与多巴酚丁胺联合治疗小儿中毒性细菌性痢疾伴休克临床观察 [J] . 刘蓉 . 中国医药卫生 . 2005,第008期

6. 中分子羟乙基淀粉(1 30／0．4)对脓毒性休克病人胃粘膜灌注的影响 [C] . 吴建浓 ,雷澍 ,方强 . 2007年浙江省医学会危重病学术年会 . 2007

7. TLR5-RA在肠粘膜固有层树突状细胞抵御创伤性失血性休克后肠道细菌移位中的作用及机制研究 [A] . 张剑 . 2017

1. 一种预防和治疗鱼类细菌和病毒性疾病的饲料添加剂 [P] . 中国专利： CN103750069B . 2015.07.15

2. 一种预防和治疗鱼类细菌和病毒性疾病的复方中草药制剂 [P] . 中国专利： CN103393778B . 2014.11.19

3. PREVENTING AND THERAPEUTIC AGENT FOR BACTERIAL TOXIC SHOCK [P] . 外国专利： JPH05155779A . 1993-06-22

机译：细菌毒性休克的预防和治疗剂

4. method for killing or inactivating microorganisms in mammalian tissue, antimicrobial composition, and method for decolonizing at least a portion of an individual's nasal cavities, anterior nostrils, and / or nasopharynx, for decolonizing at least a portion of an individual's esophageal cavity , to prevent and / or treat an affliction caused or aggravated by a microbial organism in the skin and / or mucosal membrane, to provide residual antimicrobial efficacy on a surface, to prevent and / or to treat an individual for a respiratory distress caused by a microbial infection, to treat a middle ear infection in an individual, to treat chronic sinusitis in an individual, to treat impetigo on an individual's skin, to treat and / or prevent an infection in mammalian tissue, to treat and / or prevent infection of the skin, mucosal tissue, and / or wound of an individual to provide residual antimicrobial efficacy on the skin, mucosal tissue, and / or in an individual's wound and to make an anti [P] . 外国专利： BRPI0514939A . 2008-07-01

机译：杀死或灭活哺乳动物组织中的微生物的方法，抗菌组合物，以及对至少一部分鼻腔，前鼻孔和/或鼻咽进行非殖民化的方法，以对至少一部分食道腔进行非殖民化，以防止和/或治疗由皮肤和/或粘膜中的微生物引起或加重的折磨，在表面上提供残留的抗菌功效，预防和/或治疗个体因微生物感染引起的呼吸窘迫，治疗个体中耳感染，治疗个体慢性鼻窦炎，治疗个体皮肤脓疱病，治疗和/或预防哺乳动物组织感染，治疗和/或预防皮肤，粘膜组织感染和/或个体的伤口，以在皮肤，粘膜组织和/或个体的伤口上提供残留的抗菌功效，并产生抗

5. Compositions and methods for treating and preventing pathogenic bacterial infections based on the essential role of DNA methylation in bacterial toxicity [P] . 外国专利： JP2002536339A . 2002-10-29

机译：基于DNA甲基化在细菌毒性中的重要作用的用于治疗和预防病原性细菌感染的组合物和方法

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Mucosal Tolerance to a Bacterial Superantigen Indicates a Novel Pathway To Prevent Toxic Shock

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