Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2024

Elucidation of the host transcriptomic response to pneumococcal-viral co-infection in infant mice (103943)

Hanwen Hou 1 2 , Sam Manna 1 2 3 , Odilia Wijburg 2 , Simon Phipps 4 , Catherine Satzke 1 2 5
  1. Infection and Immunity, Murdoch Children’s Research Institute, Melbourne, VIC, Australia
  2. Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
  3. Murdoch Children's Research Institute, Melbourne, VIC, Australia
  4. Respiratory Immunology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, VIC, Australia
  5. Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia

Streptococcus pneumoniae (the pneumococcus) and respiratory syncytial virus (RSV) are major causes of pneumonia. Pneumococci typically colonise the nasopharynx asymptomatically (carriage), and co-infection with viruses can lead to more severe outcomes. We previously showed pneumococcal carriage accelerated clearance of Pneumonia Virus of Mice (PVM, a murine analogue of RSV). However, the underlying mechanism of this antagonistic interaction remains unknown.

To examine host responses behind this antagonistic interaction, we extracted RNA from nasopharyngeal tissues of mice infected with pneumococci only (5 days old), PVM only (9 days old), co-infected, or mock-infected. RNA was sequenced to 30 million reads per sample in 150 bp paired-ended mode, with downstream analysis conducted using Limma (in R). Corresponding to different phases of PVM infection, host transcriptional responses were examined at 13, 17 and 21 days old.

Pneumococci alone induced a limited host response at 13 days old, with more marked transcriptional changes at 17 and 21 days old with 439 and 502 differentially expressed genes (DEGs) compared to mock-infected, respectively. An overall immune-suppressive and Th2-biased environment with Treg upregulation was observed, with limited Th1 or Th17 responses. The host response against PVM was minimal except at 17 days old (the peak of PVM replication) with 222 DEGs and a mixed Th1 and Th2 response. During co-infection, 989 and 1350 DEGs were identified, including 329 and 318 DEGs unique to co-infection (absent during any mono-infections) at 17 and 21 days old, respectively. We observed anti-inflammatory responses during pneumococcal mono-infection and co-infection, whereas such response was mostly absent during the PVM mono-infection. We hypothesise the anti-inflammatory response to pneumococcal carriage promoted the accelerated clearance of PVM during coinfection. Our work lays the foundation for examining key genes causing antagonistic bacterial-viral interactions, which could be harnessed to prevent or treat such infections.