| Title: |
DataSheet_1_Aberrant adaptive immune response underlies genetic susceptibility to tuberculosis.pdf |
| Authors: |
Anastasiia Tsareva; Pavel V. Shelyakin; Irina A. Shagina; Mikhail Yu. Myshkin; Ekaterina M. Merzlyak; Valeriia V. Kriukova; Alexander S. Apt; Irina A. Linge; Dmitriy M. Chudakov; Olga V. Britanova |
| Publication Year: |
2024 |
| Collection: |
Frontiers: Figshare |
| Subject Terms: |
Immunology; Applied Immunology (incl. Antibody Engineering; Xenotransplantation and T-cell Therapies); Autoimmunity; Cellular Immunology; Humoural Immunology and Immunochemistry; Immunogenetics (incl. Genetic Immunology); Innate Immunity; Transplantation Immunology; Tumour Immunology; Immunology not elsewhere classified; Genetic Immunology; Animal Immunology; Veterinary Immunology; TCR repertoire; tuberculosis; TB-susceptible mouse strain; CD4 + T cells; B cells; immunoglobulins; transcriptomic signatures |
| Description: |
Mycobacterium tuberculosis (Mtb) remains a major threat worldwide, although only a fraction of infected individuals develops tuberculosis (TB). TB susceptibility is shaped by multiple genetic factors, and we performed comparative immunological analysis of two mouse strains to uncover relevant mechanisms underlying susceptibility and resistance. C57BL/6 mice are relatively TB-resistant, whereas I/St mice are prone to develop severe TB, partly due to the MHC-II allelic variant that shapes suboptimal CD4 + T cell receptor repertoire. We investigated the repertoires of lung-infiltrating helper T cells and B cells at the progressed stage in both strains. We found that lung CD4 + T cell repertoires of infected C57BL/6 but not I/St mice contained convergent TCR clusters with functionally confirmed Mtb specificity. Transcriptomic analysis revealed a more prominent Th1 signature in C57BL/6, and expression of pro-inflammatory IL-16 in I/St lung-infiltrating helper T cells. The two strains also showed distinct Th2 signatures. Furthermore, the humoral response of I/St mice was delayed, less focused, and dominated by IgG/IgM isotypes, whereas C57BL/6 mice generated more Mtb antigen-focused IgA response. We conclude that the inability of I/St mice to produce a timely and efficient anti-Mtb adaptive immune responses arises from a suboptimal helper T cell landscape that also impacts the humoral response, leading to diffuse inflammation and severe disease. |
| Document Type: |
dataset |
| Language: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/DataSheet_1_Aberrant_adaptive_immune_response_underlies_genetic_susceptibility_to_tuberculosis_pdf/25792968 |
| DOI: |
10.3389/fimmu.2024.1380971.s001 |
| Availability: |
https://doi.org/10.3389/fimmu.2024.1380971.s001; https://figshare.com/articles/dataset/DataSheet_1_Aberrant_adaptive_immune_response_underlies_genetic_susceptibility_to_tuberculosis_pdf/25792968 |
| Rights: |
CC BY 4.0 |
| Accession Number: |
edsbas.C741BBA9 |
| Database: |
BASE |