霍乱毒素的黏膜佐剂活性需要 Th17 细胞，并能预防吸入性炭疽。
Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax.
机构信息
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10638-43. doi: 10.1073/pnas.1002348107. Epub 2010 May 17.
Abstract
Cholera toxin (CT) elicits a mucosal immune response in mice when used as a vaccine adjuvant. The mechanisms by which CT exerts its adjuvant effects are incompletely understood. We show that protection against inhalation anthrax by an irradiated spore vaccine depends on CT-mediated induction of IL-17-producing CD4 Th17 cells. Furthermore, IL-17 is involved in the induction of serum and mucosal antibody responses by CT. Th17 cells induced by CT have a unique cytokine profile compared with those induced by IL-6 and TGF-beta, and their induction by CT requires cAMP-dependent secretion of IL-1beta and beta-calcitonin gene-related peptide by dendritic cells. These findings demonstrate that Th17 cells mediate mucosal adjuvant effects of CT and identify previously unexplored pathways involved in Th17 induction that could be targeted for development of unique mucosal adjuvants.
摘要
霍乱毒素（CT）作为疫苗佐剂在小鼠中引发黏膜免疫应答。但其发挥佐剂作用的机制尚不完全清楚。我们发现，用辐照孢子疫苗预防吸入性炭疽依赖于 CT 介导的产生白细胞介素-17 的 CD4 Th17 细胞的诱导。此外，白细胞介素-17 参与 CT 诱导的血清和黏膜抗体应答。与由白细胞介素-6 和转化生长因子-β诱导的 Th17 细胞相比，CT 诱导的 Th17 细胞具有独特的细胞因子谱，并且 CT 诱导它们需要树突状细胞依赖 cAMP 的白细胞介素-1β和降钙素基因相关肽的分泌。这些发现表明 Th17 细胞介导 CT 的黏膜佐剂效应，并确定了以前未探索的参与 Th17 诱导的途径，这些途径可能成为开发独特黏膜佐剂的目标。
相似文献
1
Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax.霍乱毒素的黏膜佐剂活性需要 Th17 细胞，并能预防吸入性炭疽。
Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10638-43. doi: 10.1073/pnas.1002348107. Epub 2010 May 17.
2
Effective mucosal immunity to anthrax: neutralizing antibodies and Th cell responses following nasal immunization with protective antigen.对炭疽的有效黏膜免疫：用保护性抗原经鼻免疫后的中和抗体及Th细胞反应
J Immunol. 2003 Jun 1;170(11):5636-43. doi: 10.4049/jimmunol.170.11.5636.
3
Intranasal delivery of cholera toxin induces th17-dominated T-cell response to bystander antigens.经鼻递送霍乱毒素可诱导以Th17为主导的针对旁观者抗原的T细胞应答。
PLoS One. 2009;4(4):e5190. doi: 10.1371/journal.pone.0005190. Epub 2009 Apr 10.
4
Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues.参与免疫球蛋白A应答的辅助性T细胞亚群：以破伤风类毒素和霍乱毒素作为佐剂进行口服免疫，可在黏膜相关组织中选择性诱导Th2细胞。
J Exp Med. 1993 Oct 1;178(4):1309-20. doi: 10.1084/jem.178.4.1309.
5
A modified cholera holotoxin CT-E29H enhances systemic and mucosal immune responses to recombinant Norwalk virus-virus like particle vaccine.一种改良的霍乱全毒素CT-E29H可增强对重组诺如病毒样颗粒疫苗的全身和黏膜免疫反应。
Vaccine. 2003 Jan 17;21(5-6):376-85. doi: 10.1016/s0264-410x(02)00618-7.
6
Interleukin-12 alters helper T-cell subsets and antibody profiles induced by the mucosal adjuvant cholera toxin.白细胞介素-12可改变由黏膜佐剂霍乱毒素诱导的辅助性T细胞亚群及抗体谱。
Ann N Y Acad Sci. 1996 Oct 31;795:361-5. doi: 10.1111/j.1749-6632.1996.tb52693.x.
7
Sublingual targeting of STING with 3'3'-cGAMP promotes systemic and mucosal immunity against anthrax toxins.用3'3'-环状二核苷酸单磷酸（3'3'-cGAMP）进行STING的舌下靶向给药可促进针对炭疽毒素的全身和黏膜免疫。
Vaccine. 2017 Apr 25;35(18):2511-2519. doi: 10.1016/j.vaccine.2017.02.064. Epub 2017 Mar 24.
8
Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.霍乱毒素在小鼠中的黏膜佐剂效应源于T辅助2（Th2）细胞和白细胞介素-4的诱导。
J Immunol. 1995 Nov 15;155(10):4621-9.
9
Effects of cholera toxin on innate and adaptive immunity and its application as an immunomodulatory agent.霍乱毒素对固有免疫和适应性免疫的影响及其作为免疫调节剂的应用。
J Leukoc Biol. 2004 May;75(5):756-63. doi: 10.1189/jlb.1103534. Epub 2004 Jan 2.
10
ERdj5 in Innate Immune Cells Is a Crucial Factor for the Mucosal Adjuvanticity of Cholera Toxin.内质网二硫键异构酶 5 在天然免疫细胞中是霍乱毒素黏膜佐剂活性的关键因素。
Front Immunol. 2019 Jun 4;10:1249. doi: 10.3389/fimmu.2019.01249. eCollection 2019.
引用本文的文献
1
Neutrophil Extracellular Traps as a Biomarker in Refractory Non-Type 2 CRSwNP.中性粒细胞胞外诱捕网作为难治性非2型慢性鼻-鼻窦炎伴鼻息肉的生物标志物
Allergy Asthma Immunol Res. 2024 Sep;16(5):473-489. doi: 10.4168/aair.2024.16.5.473.
2
Role of cellular effectors in the induction and maintenance of IgA responses leading to protective immunity against enteric bacterial pathogens.细胞效应因子在诱导和维持 IgA 反应中的作用，这些反应导致对肠道细菌病原体的保护性免疫。
Front Immunol. 2024 Sep 11;15:1446072. doi: 10.3389/fimmu.2024.1446072. eCollection 2024.
3
ER-transiting bacterial toxins amplify STING innate immune responses and elicit ER stress.内质网转位细菌毒素放大 STING 固有免疫反应并引发内质网应激。
Infect Immun. 2024 Aug 13;92(8):e0030024. doi: 10.1128/iai.00300-24. Epub 2024 Jul 26.
4
All roads lead to IgA: Mapping the many pathways of IgA induction in the gut.条条大路通IgA：探寻肠道中IgA诱导的多种途径
Immunol Rev. 2024 Sep;326(1):66-82. doi: 10.1111/imr.13369. Epub 2024 Jul 24.
5
Vaccine Strategies to Elicit Mucosal Immunity.诱导黏膜免疫的疫苗策略。
Vaccines (Basel). 2024 Feb 13;12(2):191. doi: 10.3390/vaccines12020191.
6
cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.cAMP-PKA/EPAC 信号转导与癌症：肿瘤微环境中的相互作用。
J Hematol Oncol. 2024 Jan 17;17(1):5. doi: 10.1186/s13045-024-01524-x.
7
Non-mucosal vaccination strategies to enhance mucosal immunity.增强黏膜免疫力的非黏膜疫苗接种策略。
Vaccine Insights. 2023 Jul;2(6):229-236. doi: 10.18609/vac.2023.034. Epub 2023 Jul 12.
8
, classification, pathogenesis, immune response, and trends in vaccine development.分类、发病机制、免疫反应及疫苗研发趋势。
Front Med (Lausanne). 2023 May 5;10:1155751. doi: 10.3389/fmed.2023.1155751. eCollection 2023.
9
Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines.黏膜佐剂经黏膜黏附贴片经舌下给药用于亚单位疫苗。
Int J Mol Sci. 2022 Nov 3;23(21):13440. doi: 10.3390/ijms232113440.
10
Enhanced Immunogenicity of Adjuvanted Microparticulate HPV16 Vaccines Administered via the Transdermal Route.经皮给药的佐剂化微粒人乳头瘤病毒16型疫苗的免疫原性增强
Pharmaceuticals (Basel). 2022 Sep 9;15(9):1128. doi: 10.3390/ph15091128.
本文引用的文献
1
Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus.白细胞介素17与B细胞活化因子协同作用，影响B细胞生物学及系统性红斑狼疮的病理生理学。
Nat Immunol. 2009 Jul;10(7):778-85. doi: 10.1038/ni.1741. Epub 2009 May 31.
2
Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion.前列腺素E2-EP4信号通路通过Th1细胞分化和Th17细胞扩增促进免疫炎症。
Nat Med. 2009 Jun;15(6):633-40. doi: 10.1038/nm.1968.
3
Critical regulation of early Th17 cell differentiation by interleukin-1 signaling.白细胞介素-1信号对早期辅助性T细胞17分化的关键调控
Immunity. 2009 Apr 17;30(4):576-87. doi: 10.1016/j.immuni.2009.02.007. Epub 2009 Apr 9.
4
Intranasal delivery of cholera toxin induces th17-dominated T-cell response to bystander antigens.经鼻递送霍乱毒素可诱导以Th17为主导的针对旁观者抗原的T细胞应答。
PLoS One. 2009;4(4):e5190. doi: 10.1371/journal.pone.0005190. Epub 2009 Apr 10.
5
Cutting edge: lung mucosal Th17-mediated responses induce polymeric Ig receptor expression by the airway epithelium and elevate secretory IgA levels.前沿：肺黏膜Th17介导的反应诱导气道上皮表达多聚免疫球蛋白受体并提高分泌型IgA水平。
J Immunol. 2009 Apr 15;182(8):4507-11. doi: 10.4049/jimmunol.0900237.
6
Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling.前列腺素E2通过环磷酸腺苷和EP2/EP4受体信号传导调节Th17细胞的分化和功能。
J Exp Med. 2009 Mar 16;206(3):535-48. doi: 10.1084/jem.20082293. Epub 2009 Mar 9.
7
Interleukin-17 is a critical mediator of vaccine-induced reduction of Helicobacter infection in the mouse model.白细胞介素-17是小鼠模型中疫苗诱导的幽门螺杆菌感染减少的关键介质。
Gastroenterology. 2009 Jun;136(7):2237-2246.e1. doi: 10.1053/j.gastro.2009.02.077. Epub 2009 Mar 9.
8
Protection against Pneumococcal colonization and fatal pneumonia by a trivalent conjugate of a fusion protein with the cell wall polysaccharide.一种融合蛋白与细胞壁多糖的三价结合物对肺炎球菌定植和致死性肺炎的保护作用。
Infect Immun. 2009 May;77(5):2076-83. doi: 10.1128/IAI.01554-08. Epub 2009 Mar 2.
9
IL-17 and Th17 Cells.白细胞介素-17与辅助性T细胞17
Annu Rev Immunol. 2009;27:485-517. doi: 10.1146/annurev.immunol.021908.132710.
10
ATP drives lamina propria T(H)17 cell differentiation.三磷酸腺苷驱动固有层辅助性T细胞17分化。
Nature. 2008 Oct 9;455(7214):808-12. doi: 10.1038/nature07240. Epub 2008 Aug 20.
Zotero 插件