RSV-NTHi Co-Infection Skews Host Immunity by Suppressing Type I IFN Responses and Enhancing Pro-Inflammatory...

Area of Science:

• Pediatric infectious diseases
• Virology
• Immunology

Background:

• Respiratory syncytial virus (RSV) causes significant lower respiratory tract disease in infants.
• The mechanisms linking RSV severity to host immune responses and bacterial co-infections are not fully understood.
• Defective viral genomes (DVGs) are potent inducers of type I/III interferons (IFNs), crucial for antiviral defense.

Purpose of the Study:

• To investigate the impact of nontypeable Haemophilus influenzae (NTHi) on RSV replication and host immune responses during co-infection.
• To elucidate the mechanisms by which NTHi influences RSV disease severity in a clinically relevant model.

Main Methods:

• Concurrent RSV-NTHi co-infection experiments were performed in vitro using A549 cells and ex vivo using human precision-cut lung slices.
• RSV titers, NTHi abundance, DVG replication, and host IFN and inflammatory cytokine responses were measured.

Main Results:

• Co-infection led to reduced RSV titers but not NTHi titers.
• Extracellular NTHi inhibited RSV binding to host cells.
• RSV-NTHi co-infection suppressed DVG replication and DVG-driven IFN responses but enhanced inflammatory signaling, potentially due to increased cell-associated NTHi.

Conclusions:

• NTHi exacerbates RSV disease severity by dysregulating host immune responses, leading to suppressed antiviral defenses and enhanced inflammation.
• These findings provide a mechanistic understanding of how bacterial co-infections complicate viral respiratory illnesses.