Aberrant adaptive immune response underlies genetic susceptibility to tuberculosis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F24%3A00138870" target="_blank" >RIV/00216224:14740/24:00138870 - isvavai.cz</a>
Result on the web
<a href="https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1380971/full" target="_blank" >https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1380971/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fimmu.2024.1380971" target="_blank" >10.3389/fimmu.2024.1380971</a>
Alternative languages
Result language
angličtina
Original language name
Aberrant adaptive immune response underlies genetic susceptibility to tuberculosis
Original language 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in immunology
ISSN
1664-3224
e-ISSN
1664-3224
Volume of the periodical
15
Issue of the periodical within the volume
May
Country of publishing house
CH - SWITZERLAND
Number of pages
12
Pages from-to
1-12
UT code for WoS article
001229860400001
EID of the result in the Scopus database
2-s2.0-85193956917