Branchett, William J;
Stavropoulos, Evangelos;
Shields, Jessica;
Al-Dibouni, Alaa;
Cardoso, Marcos;
Fernandes, Ana Isabel;
Moreira-Teixeira, Lucia;
... O'Garra, Anne; + view all
(2025)
Type I IFN drives neutrophil swarming, impeding lung T cell–macrophage interactions and TB control.
Journal of Experimental Medicine
, 222
(12)
, Article e20250466. 10.1084/jem.20250466.
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Abstract
The early immune mechanisms determining Mycobacterium tuberculosis infection outcome are unclear. Using bulk and scRNA-seq over the first weeks of infection, we describe an unexpected, higher early pulmonary type I IFN response in relatively resistant C57BL/6 as compared with highly TB-susceptible C3HeB/FeJ mice. C57BL/6 mice showed pronounced early monocyte-derived macrophage (MDM) accumulation and extensive CD4+ T cell-MDM interactions in lung lesions, accompanied by high expression of T cell-attractant chemokines by MDMs. Conversely, lesions in C3HeB/FeJ mice were dominated by neutrophils with high expression of pro-inflammatory chemokines, from which CD4+ T cells were spatially segregated. Early type I IFN signaling blockade reduced bacterial load and neutrophil swarming within early TB lesions while increasing CD4+ T cell numbers in both C57BL/6 and C3HeB/FeJ mice, with later more pronounced effects on bacterial load in C3HeB/FeJ mice. These data suggest that early type I IFN signaling during M. tuberculosis infection favors neutrophil accumulation and limits CD4+ T cell infiltration into developing lesions.
| Type: | Article |
|---|---|
| Title: | Type I IFN drives neutrophil swarming, impeding lung T cell–macrophage interactions and TB control |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1084/jem.20250466 |
| Publisher version: | https://doi.org/10.1084/jem.20250466 |
| Language: | English |
| Additional information: | © 2025 Branchett et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/ by/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10217915 |
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