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Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model.

Publication ,  Journal Article
Church, EC; Bishop, E; Fiore-Gartland, A; Yu, KKQ; Chang, M; Jones, RM; Brache, JK; Ballweber Fleming, L; Phan, JM; Makatsa, MS; Heptinstall, J ...
Published in: Immunohorizons
September 1, 2024

Cutaneous mycobacterial infections cause substantial morbidity and are challenging to diagnose and treat. An improved understanding of the dermal immune response to mycobacteria may inspire new therapeutic approaches. We conducted a controlled human infection study with 10 participants who received 2 × 106 CFUs of Mycobacterium bovis bacillus Calmette-Guérin (Tice strain) intradermally and were randomized to receive isoniazid or no treatment. Peripheral blood was collected at multiple time points for flow cytometry, bulk RNA sequencing (RNA-seq), and serum Ab assessments. Systemic immune responses were detected as early as 8 d postchallenge in this M. bovis bacillus Calmette-Guérin-naive population. Injection-site skin biopsies were performed at days 3 and 15 postchallenge and underwent immune profiling using mass cytometry and single-cell RNA-seq, as well as quantitative assessments of bacterial viability and burden. Molecular viability testing and standard culture results correlated well, although no differences were observed between treatment arms. Single-cell RNA-seq revealed various immune and nonimmune cell types in the skin, and communication between them was inferred by ligand-receptor gene expression. Day 3 communication was predominantly directed toward monocytes from keratinocyte, muscle, epithelial, and endothelial cells, largely via the migration inhibitory factor pathway and HLA-E-KLRK1 interaction. At day 15, communication was more balanced between cell types. These data reveal the potential role of nonimmune cells in the dermal immune response to mycobacteria and the utility of human challenge studies to augment our understanding of mycobacterial infections.

Duke Scholars

Published In

Immunohorizons

DOI

EISSN

2573-7732

Publication Date

September 1, 2024

Volume

8

Issue

9

Start / End Page

695 / 711

Location

United States

Related Subject Headings

  • Young Adult
  • Tuberculosis
  • Skin
  • Mycobacterium bovis
  • Male
  • Isoniazid
  • Humans
  • Female
  • Antitubercular Agents
  • Adult
 

Citation

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ICMJE
MLA
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Church, E. C., Bishop, E., Fiore-Gartland, A., Yu, K. K. Q., Chang, M., Jones, R. M., … Seshadri, C. (2024). Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model. Immunohorizons, 8(9), 695–711. https://doi.org/10.4049/immunohorizons.2400053
Church, E Chandler, Emma Bishop, Andrew Fiore-Gartland, Krystle K. Q. Yu, Ming Chang, Richard M. Jones, Justin K. Brache, et al. “Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model.Immunohorizons 8, no. 9 (September 1, 2024): 695–711. https://doi.org/10.4049/immunohorizons.2400053.
Church EC, Bishop E, Fiore-Gartland A, Yu KKQ, Chang M, Jones RM, et al. Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model. Immunohorizons. 2024 Sep 1;8(9):695–711.
Church, E. Chandler, et al. “Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model.Immunohorizons, vol. 8, no. 9, Sept. 2024, pp. 695–711. Pubmed, doi:10.4049/immunohorizons.2400053.
Church EC, Bishop E, Fiore-Gartland A, Yu KKQ, Chang M, Jones RM, Brache JK, Ballweber Fleming L, Phan JM, Makatsa MS, Heptinstall J, Chiong K, Dintwe O, Naidoo A, Voillet V, Mayer-Blackwell K, Nwanne G, Andersen-Nissen E, Vary JC, Tomaras GD, McElrath MJ, Sherman DR, Murphy SC, Kublin JG, Seshadri C. Probing Dermal Immunity to Mycobacteria through a Controlled Human Infection Model. Immunohorizons. 2024 Sep 1;8(9):695–711.

Published In

Immunohorizons

DOI

EISSN

2573-7732

Publication Date

September 1, 2024

Volume

8

Issue

9

Start / End Page

695 / 711

Location

United States

Related Subject Headings

  • Young Adult
  • Tuberculosis
  • Skin
  • Mycobacterium bovis
  • Male
  • Isoniazid
  • Humans
  • Female
  • Antitubercular Agents
  • Adult