Influenza-induced activation of recruited alveolar macrophages during the early inflammatory phase drives lung injury and lethality
Clarissa M Koch,
Jennifer Yuan-Shi Hu,
Bria M Coates,
Paul A. Reyfman,
Alexander V. Misharin,
GR Scott Budinger,
Deborah R. Winter,
Karen M. Ridge
Posted 09 Jun 2020
bioRxiv DOI: 10.1101/2020.06.08.141309
Posted 09 Jun 2020
Influenza A virus (IAV) infection significantly contributes to global mortality each year. Previous studies have shown that monocyte-derived alveolar macrophages recruited to the lung drive injury during influenza infection. However, the exact timing and mechanism of macrophage-driven lung damage is unknown. Here, we define three distinct patterns of gene expression in recruited macrophages over the first six days post-IAV infection in mice. Additionally, we demonstrate that Vim-/- mice infected with IAV exhibit decreased mortality, which was associated with a temporally altered transcriptional response in recruited macrophages. During the early inflammatory phase of IAV response, Vim-/- macrophages were characterized by a protective shift in macrophage activation. Furthermore, using a bone-marrow chimera mouse model, we demonstrate that vimentin deficiency in recruited macrophages is sufficient to confer protection from IAV-induced mortality. Taken together, our findings provide new insight into the temporal dynamics of macrophage function in response to IAV infection. ### Competing Interest Statement The authors have declared no competing interest.
- Downloaded 174 times
- Download rankings, all-time:
- Site-wide: 83,389 out of 101,163
- In immunology: 2,485 out of 3,151
- Year to date:
- Site-wide: 35,175 out of 101,163
- Since beginning of last month:
- Site-wide: 28,287 out of 101,163
Downloads over time
Distribution of downloads per paper, site-wide
- 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!