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Dual RNASeq Reveals NTHi-Macrophage Transcriptomic Changes During Intracellular Persistence
Jodie Ackland1, Ashley I Heinson1, David W Cleary1,2
1Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Frontiers in Cellular and Infection Microbiology
|September 9, 2021
Summary
Nontypeable Haemophilus influenzae (NTHi) persists in human macrophages by altering its gene expression. Targeting these bacterial adaptations offers a potential strategy against chronic respiratory infections.
Area of Science:
- Microbiology
- Immunology
- Genomics
Background:
- Nontypeable Haemophilus influenzae (NTHi) is a significant cause of chronic respiratory disease, often persisting in airways.
- Evidence suggests NTHi invades and survives within host macrophages, but the mechanisms remain unclear.
Purpose of the Study:
- To investigate the transcriptomic adaptations of NTHi during intracellular persistence within human macrophages.
- To elucidate the host-pathogen interactions facilitating NTHi survival.
Main Methods:
- Development of an in vitro model using human monocyte-derived macrophages (MDM) and NTHi.
- Application of Dual RNA Sequencing to simultaneously analyze host and bacterial gene expression.
- Bioinformatic analyses including gene list enrichment and KEGG pathway analysis.
Main Results:
- Identification of temporally regulated host and bacterial transcriptomic profiles during NTHi persistence.
- Discovery of a conserved 'core' macrophage gene expression profile enriched for immune response pathways.
- NTHi persistence involved modulation of bacterial metabolic, stress response, and ribosome pathways, with distinct gene expression compared to planktonic bacteria.
Conclusions:
- NTHi exhibits specific transcriptomic adaptations for intracellular survival within macrophages.
- Understanding these adaptations provides insights into chronic NTHi colonization.
- Targeting identified bacterial pathways may offer novel therapeutic strategies against NTHi-associated respiratory diseases.
