Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Type I interferons (IFN-I) increase susceptibility to bacterial superinfections, a significant clinical challenge during viral infections or interferon-alpha (IFN-α) therapy.
• IFN-I-induced neutropenia contributes to impaired bacterial control, but bacterial infections during IFN-α treatment can occur independently of neutropenia.

Purpose of the Study:

• To investigate the impact of viral co-infection on the control of Pseudomonas aeruginosa infection.
• To elucidate the mechanisms by which Type I interferon influences bacterial clearance in a mouse model.

Main Methods:

• A mouse model was used to assess Pseudomonas aeruginosa control during co-infection with lymphocytic choriomeningitis virus (LCMV).
• Bacterial titers, neutrophil counts, and liver-lysozyme-2 gene expression were measured in wild-type and Ifnar(-/-) mice infected with P. aeruginosa, with or without LCMV or poly(I:C) administration.

Main Results:

• Virus-induced IFN-I significantly impaired Pseudomonas aeruginosa control, correlating with neutropenia and reduced liver-lysozyme-2 expression.
• Lower IFN-I levels, induced by poly(I:C) or by virulent P. aeruginosa alone, also compromised bacterial control and lysozyme-2 expression in the liver.
• The cooperative interaction between Kupffer cells and neutrophils for bacterial clearance was disrupted during LCMV co-infection.

Conclusions:

• Type I interferon plays a critical role in controlling systemic P. aeruginosa infections.
• Viral infections disrupt the innate immune response, specifically the Kupffer cell-neutrophil cooperation, leading to impaired bacterial clearance.
• Interferon therapy or viral infections can exacerbate bacterial infections through mechanisms beyond neutropenia.