Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection

Johanna M. Sweere, Jonas D. Van Belleghem, Heather Ishak, Michelle S. Bach, Medeea Popescu, Vivekananda Sunkari, Gernot Kaber, Robert Manasherob, Gina A. Suh, Xiou Cao, Christiaan R. de Vries, Dung N. Lam, Payton L. Marshall, Maria Birukova, Ethan Katznelson, Daniel V. Lazzareschi, Swathi Balaji, Sundeep G. Keswani, Thomas R. Hawn, Patrick R. SecorPaul L. Bollyky

Research output: Contribution to journalArticlepeer-review

Abstract

Bacteriophage are abundant at sites of bacterial infection, but their effects on mammalian hosts are unclear. We have identified pathogenic roles for filamentous Pf bacteriophage produced by Pseudomonas aeruginosa (Pa) in suppression of immunity against bacterial infection. Pf promote Pa wound infection in mice and are associated with chronic human Pa wound infections. Murine and human leukocytes endocytose Pf, and internalization of this single-stranded DNA virus results in phage RNA production. This triggers Toll-like receptor 3 (TLR3)– and TIR domain–containing adapter-inducing interferon-b (TRIF)–dependent type I interferon production, inhibition of tumor necrosis factor (TNF), and the suppression of phagocytosis. Conversely, immunization of mice against Pf prevents Pa wound infection. Thus, Pf triggers maladaptive innate viral pattern-recognition responses, which impair bacterial clearance. Vaccination against phage virions represents a potential strategy to prevent bacterial infection.

Original languageEnglish
Article numbereaat9691
JournalScience
Volume363
Issue number6434
DOIs
StatePublished - Mar 29 2019

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