Abstract
Alveolar macrophages act as an early viral sponge inducing long-lived functional enhancement
The Journal of immunology (1950), Vol.208(1_Supplement), pp.126-126.05
05/01/2022
DOI: 10.4049/jimmunol.208.Supp.126.05
Abstract
Abstract Alveolar macrophages (AM) are one of the first immune cells to encounter pathogens in the lung. However, the role of AMs early after infection remains to be completely defined. To track virally infected cells, mice were infected with a panel of fluorescent reporter-expressing respiratory viruses. By 6 hr post-infection (p.i.), AM numbers significantly declined. The remaining AMs accounted for the majority of infected cells at early time points, surpassing the epithelium, but did not support significant viral replication. Strikingly, AMs represented over 80% of all respiratory syncytial virus (RSV)-infected cells which was confirmed by intravital microscopy and ImageStream flow cytometry. To track cells that survive infection, we utilized a novel cre recombinase-expressing RSV in a floxed-reporter mouse in which infected cells are indelibly marked. Cre-mediated reporter activation required direct infection, and reporter-positive AM numbers remained constant up to 30 days p.i., long after viral clearance. Reporter-positive and -negative AMs were isolated at 30 days p.i., and their functional capacity was assessed ex vivo. Both reporter-positive and -negative AMs exhibited increased basal levels of pro-inflammatory cytokines as compared to naïve AMs which was further increased upon heterologous infection. Reporter-positive AMs displayed an enhanced inflammatory response as compared to reporter-negative AMs from the same lung, indicating innate immunity can be further increased post-direct infection. Our results confirm that AMs play an essential role in limiting early viral access to the respiratory epithelium by serving as a reservoir for non-productive infection resulting in long-lived functional enhancement. Supported by grants from NIH (R01AI124093-01A1, T32AI007485) and fellowships from NASA (Iowa Space Grant Consortium) and the University of Iowa Graduate College.
Details
- Title: Subtitle
- Alveolar macrophages act as an early viral sponge inducing long-lived functional enhancement
- Creators
- Kody WaldsteinStephanie van de WallScott AnthonyJohn T HartySteven M Varga
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.208(1_Supplement), pp.126-126.05
- DOI
- 10.4049/jimmunol.208.Supp.126.05
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2022
- Academic Unit
- Pathology; Microbiology and Immunology; Otolaryngology
- Record Identifier
- 9984354960202771
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