Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

T cell transcription factor expression evolves as adaptive immunity matures in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques

Nicole L. Grant, Pauline Maiello, Edwin Klein, Philana Ling Lin, H. Jacob Borish, Jaime Tomko, L. James Frye, Alexander G. White, Denise E. Kirschner, Joshua T. Mattila, JoAnne L. Flynn
doi: https://doi.org/10.1101/2022.01.25.477732
Nicole L. Grant
1Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pauline Maiello
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edwin Klein
3Division of Laboratory Animal Research, University of Pittsburgh, Pittsburgh PA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philana Ling Lin
4Department of Pediatrics, Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America
5Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H. Jacob Borish
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jaime Tomko
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. James Frye
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander G. White
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Denise E. Kirschner
6Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joshua T. Mattila
1Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States of America
5Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
JoAnne L. Flynn
2Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America
5Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: joanne@pitt.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

SUMMARY

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understanding host control of bacterial replication. We identified and compared the pathological, cellular, and functional differences in granulomas at 4, 12, and 20 weeks post-infection in Chinese cynomolgus macaques. Original granulomas differed in transcription factor expression within adaptive lymphocytes with those at 12 weeks showing higher frequencies of CD8+T-bet+ T cells, while increases in CD4+T-bet+ T cells were observed at 20 weeks post-infection. The appearance of T-bet+ adaptive T cells at 12 and 20 weeks was coincident with a reduction in bacterial burden, suggesting their critical role in Mtb control. This study highlights the evolution of T cell responses within lung granulomas, suggesting that vaccines promoting the development and migration of T-bet+ T cells would enhance mycobacterial control.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Competing Interests: Authors from the University of Pittsburgh and University of Michigan have no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted January 26, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
T cell transcription factor expression evolves as adaptive immunity matures in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
T cell transcription factor expression evolves as adaptive immunity matures in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques
Nicole L. Grant, Pauline Maiello, Edwin Klein, Philana Ling Lin, H. Jacob Borish, Jaime Tomko, L. James Frye, Alexander G. White, Denise E. Kirschner, Joshua T. Mattila, JoAnne L. Flynn
bioRxiv 2022.01.25.477732; doi: https://doi.org/10.1101/2022.01.25.477732
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
T cell transcription factor expression evolves as adaptive immunity matures in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques
Nicole L. Grant, Pauline Maiello, Edwin Klein, Philana Ling Lin, H. Jacob Borish, Jaime Tomko, L. James Frye, Alexander G. White, Denise E. Kirschner, Joshua T. Mattila, JoAnne L. Flynn
bioRxiv 2022.01.25.477732; doi: https://doi.org/10.1101/2022.01.25.477732

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3571)
  • Biochemistry (7514)
  • Bioengineering (5473)
  • Bioinformatics (20664)
  • Biophysics (10250)
  • Cancer Biology (7925)
  • Cell Biology (11563)
  • Clinical Trials (138)
  • Developmental Biology (6558)
  • Ecology (10129)
  • Epidemiology (2065)
  • Evolutionary Biology (13526)
  • Genetics (9493)
  • Genomics (12784)
  • Immunology (7869)
  • Microbiology (19429)
  • Molecular Biology (7609)
  • Neuroscience (41854)
  • Paleontology (306)
  • Pathology (1252)
  • Pharmacology and Toxicology (2178)
  • Physiology (3247)
  • Plant Biology (6993)
  • Scientific Communication and Education (1290)
  • Synthetic Biology (1941)
  • Systems Biology (5404)
  • Zoology (1107)