Distinct Gene Programs Underpinning ‘Disease Tolerance’ and ‘Resistance’ Against Infections

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Identifies two co-activated lung gene programs — T program (disease tolerance) and R program (pathogen resistance) — from ~250 samples across 33 CC mouse strains with five time points, using autoencoder-based gene-level dimension reduction. R genes map to interferon/antiviral pathways and track viral burden; T genes map to wound healing/ECM and predict tissue damage per virus. Perturbation of RGDIA affects T-specific responses, T scores before infection predict severity and replicate in BxD mice and human cohorts.

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" chapters (11)

1. 0:00Intro
2. 1:35Different individuals show distinct disease outcomes
3. 1:48Study design Lung
4. 4:29Variation in disease tolerance
5. 5:59Two key programs of the host response to IAV infection
6. 7:22Scores for the two programs successfully describe a large part of the
7. 10:41Two defense strategies: disease tolerance and resistance
8. 12:50Evidence 1: Functional analysis
9. 16:57Identification of known and putative regulators
10. 20:15Acknowledgements
11. 22:21Severity of infection is associated with elevated baseline tolerance