دورية أكاديمية
Treponema pallidum Periplasmic and Membrane Proteins Are Recognized by Circulating and Skin CD4+ T Cells.
| العنوان: | Treponema pallidum Periplasmic and Membrane Proteins Are Recognized by Circulating and Skin CD4+ T Cells. |
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| المؤلفون: | Reid TB; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Godornes C; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Campbell VL; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Laing KJ; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Tantalo LC; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Gomez A; Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada., Pholsena TN; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Lieberman NAP; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA., Krause TM; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Cegielski VI; Department of Medicine, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA., Culver LA; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Nguyen N; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Tong DQ; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA., Hawley KL; Department of Medicine and Pediatrics, UConn Health, Farmington, Connecticut, USA.; Division of Infectious Diseases, Connecticut Children's, Hartford, Connecticut, USA., Greninger AL; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Giacani L; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.; Department of Global Health, University of Washington, Seattle, Washington, USA., Cameron CE; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.; Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada., Dombrowski JC; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.; Department of Epidemiology, University of Washington School of Medicine, Seattle, Washington, USA., Wald A; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Department of Global Health, University of Washington, Seattle, Washington, USA.; Department of Epidemiology, University of Washington School of Medicine, Seattle, Washington, USA., Koelle DM; Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Department of Global Health, University of Washington, Seattle, Washington, USA.; Center for Translational Immunology, Benaroya Research Institute, Seattle, Washington, USA. |
| المصدر: | The Journal of infectious diseases [J Infect Dis] 2024 Aug 16; Vol. 230 (2), pp. 281-292. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Oxford : Oxford University Press Original Publication: 1904-2010 : Chicago, IL : University of Chicago Press |
| مواضيع طبية MeSH: | Treponema pallidum*/immunology , CD4-Positive T-Lymphocytes*/immunology , Syphilis*/immunology , Skin*/immunology , Skin*/microbiology, Humans ; Adult ; Male ; Female ; Membrane Proteins/immunology ; Antigens, Bacterial/immunology ; Middle Aged ; Interferon-gamma/metabolism ; Bacterial Proteins/immunology ; Enzyme-Linked Immunospot Assay ; Leukocytes, Mononuclear/immunology ; Young Adult |
| مستخلص: | Background: Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum-specific CD4+ T-cell responses to T. pallidum infection. We hypothesized that T. pallidum-specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment. Methods: Peripheral blood mononuclear cells collected from 67 participants were screened by interferon-γ (IFN-γ) ELISPOT response to T. pallidum sonicate. T. pallidum-reactive T-cell lines from blood and skin were probed for responses to 89 recombinant T. pallidum antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens. Results: We detected CD4+ T-cell responses to T. pallidum sonicate ex vivo. Using T. pallidum-reactive T-cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy, T. pallidum-specific T cells persisted for at least 6 months in skin and 10 years in blood. Conclusions: T. pallidum infection elicits an antigen-specific CD4+ T-cell response in blood and skin. T. pallidum-specific CD4+ T cells persist as memory in both compartments long after curative therapy. The T. pallidum antigenic targets we identified may be high-priority vaccine candidates. Competing Interests: Potential conflicts of interest . D. M. K. reports membership on the Scientific Advisory Board of MaxHealth, LLC and Curevo Vaccines; grant support from Sanofi Pasteur; and coinventorship of institutionally owned patents concerning HSV vaccines. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Presented in part: “Treponema pallidum specific CD4+ T cell epitope discovery.” AAI Immunology 2022, Portland, OR, May 2022. “Treponema pallidum-specific human CD4v T cell antigens and epitopes.” Gordon Research Symposium on the Biology of Spirochetes, Ventura, CA, June 2022. “Discovery of T. pallidum specific human CD4v T cell antigens and epitopes.” NIH STI CRC Annual National Meeting, virtual, July 2022. “Treponema pallidum-specific memory T cells persist in skin after secondary syphilis.” STI and HIV World Congress, Chicago, IL, July 2023. “Treponema pallidum periplasmic and membrane proteins are recognized by circulating and skin CD4+ T cells.” Gordon Research Conference on the Biology of Spirochetes, Ventura, CA, January 2024. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| التعليقات: | Update of: bioRxiv. 2024 Feb 29:2024.02.27.581790. doi: 10.1101/2024.02.27.581790. (PMID: 38464313) Comment in: J Infect Dis. 2024 Aug 16;230(2):275-277. doi: 10.1093/infdis/jiae246. (PMID: 39147388) |
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| معلومات مُعتمدة: | UL1 TR002319 United States TR NCATS NIH HHS; National Institute of Allergy and Infectious Diseases; U19AI144133 United States NH NIH HHS |
| فهرسة مساهمة: | Keywords: CD4+ T cell; interferon-γ; secondary syphilis; syphilis; tissue-resident memory T cell; vaccine |
| المشرفين على المادة: | 0 (Membrane Proteins) 0 (Antigens, Bacterial) 82115-62-6 (Interferon-gamma) 0 (Bacterial Proteins) |
| SCR Disease Name: | Syphilis, secondary |
| تواريخ الأحداث: | Date Created: 20240627 Date Completed: 20240815 Latest Revision: 20240817 |
| رمز التحديث: | 20240817 |
| مُعرف محوري في PubMed: | PMC11326851 |
| DOI: | 10.1093/infdis/jiae245 |
| PMID: | 38932740 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1537-6613 |
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| DOI: | 10.1093/infdis/jiae245 |