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Abstract

A Clinically Relevant Cationic Adjuvant System Induces Th17 T Cells Involved in Skin and Upper Airway Infections with Streptococcus pyogenes †

by
Kristoffer Mazanti Melchiors
*,
Nina Dieu Nhien Tran Nguyen
,
Sharmila Subratheepam
,
Ida Rosenkrands
,
Frank Follmann
and
Jes Dietrich
Statens Serum Institut, 2300 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Presented at the 22nd Lancefield International Symposium on Streptococci and Streptococcal Diseases, Brisbane, Australia, 1–5 June 2025.
Proceedings 2025, 124(1), 3; https://doi.org/10.3390/proceedings2025124003
Published: 6 August 2025

Abstract

Streptococcus pyogenes (Group A Streptococcus, StrepA) is a human pathogen responsible for hundreds of millions of infections each year and remains one of the most prevalent bacterial causes of upper respiratory and skin infections worldwide. Despite its global impact, there is no approved vaccine, and the optimal protective immune response is still not fully understood. In particular, the role of Th17 T cells in immunity against StrepA remains to be explored. We have previously shown that Th17 T cells are induced in humans following StrepA infection. In this study, we investigated the role of Th17 T cells during skin and upper airway StrepA infections. To generate StrepA-specific Th17 T cells, we utilized a novel cationic liposomal adjuvant system. We demonstrated that vaccine-induced Th17 T cells are recruited to the skin and upper airways upon StrepA infection. In the airways, Th17 T cells and IgA correlate with protection, whereas Th1 T cells and IgG do not. To further characterize the recruited Th17 T cells, we used an IL-17 fate-reporter mouse model to track Th17 T cells. Our results show that Th17 T cells outnumber bona fide Th1 T cells in both StrepA-infected skin and upper airways. Surprisingly, most Th17 T cells lose expression of IL-17, and do not express TNFα, IFNγ, and IL-2. Initial single-cell sequencing data suggest the existence of multiple Th17 T cell subsets with distinct expression profiles. We discuss the functional relevance of these subsets in the context of a StrepA infection.

Author Contributions

Conceptualization, J.D., K.M.M., N.D.N.T.N. and F.F.; methodology, J.D., K.M.M. and N.D.N.T.N.; investigation, K.M.M., N.D.N.T.N., S.S. and I.R.; formal analysis, J.D., K.M.M., N.D.N.T.N. and S.S.; supervision, J.D. and F.F.; writing—original draft preparation, K.M.M.; writing—review and editing, J.D., K.M.M., N.D.N.T.N., S.S., I.R. and F.F. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by the Leo Foundation.

Institutional Review Board Statement

The animal study protocol was approved by the Institutional Review Board (Ethics Committee) of Statens Serum Institut, IACUC, headed by DVM Kristin Engelhardt Illigen (permit number 2022-15-0201-01237, approved by the Danish Animal Experiments Inspectorate). All experiments were conducted in accordance with the regulations set forth by the Danish Ministry of Justice and the Danish Animal Experiments Inspectorate, and in compliance with European Directive 2010/63/EU and Directive 86/609, as well as the U.S. Association for Laboratory Animal Care guidelines for the care and use of laboratory animals.

Informed Consent Statement

Not relevant for this study.

Data Availability Statement

The data generated during the study are available from the corresponding author on request.

Conflicts of Interest

The authors declare no conflict of interest.
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Share and Cite

MDPI and ACS Style

Melchiors, K.M.; Nguyen, N.D.N.T.; Subratheepam, S.; Rosenkrands, I.; Follmann, F.; Dietrich, J. A Clinically Relevant Cationic Adjuvant System Induces Th17 T Cells Involved in Skin and Upper Airway Infections with Streptococcus pyogenes. Proceedings 2025, 124, 3. https://doi.org/10.3390/proceedings2025124003

AMA Style

Melchiors KM, Nguyen NDNT, Subratheepam S, Rosenkrands I, Follmann F, Dietrich J. A Clinically Relevant Cationic Adjuvant System Induces Th17 T Cells Involved in Skin and Upper Airway Infections with Streptococcus pyogenes. Proceedings. 2025; 124(1):3. https://doi.org/10.3390/proceedings2025124003

Chicago/Turabian Style

Melchiors, Kristoffer Mazanti, Nina Dieu Nhien Tran Nguyen, Sharmila Subratheepam, Ida Rosenkrands, Frank Follmann, and Jes Dietrich. 2025. "A Clinically Relevant Cationic Adjuvant System Induces Th17 T Cells Involved in Skin and Upper Airway Infections with Streptococcus pyogenes" Proceedings 124, no. 1: 3. https://doi.org/10.3390/proceedings2025124003

APA Style

Melchiors, K. M., Nguyen, N. D. N. T., Subratheepam, S., Rosenkrands, I., Follmann, F., & Dietrich, J. (2025). A Clinically Relevant Cationic Adjuvant System Induces Th17 T Cells Involved in Skin and Upper Airway Infections with Streptococcus pyogenes. Proceedings, 124(1), 3. https://doi.org/10.3390/proceedings2025124003

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