Format

Send to

Choose Destination
Science. 2019 Mar 29;363(6434). pii: eaat9691. doi: 10.1126/science.aat9691.

Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection.

Author information

1
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
2
Stanford Immunology, Stanford University, Stanford, CA, USA.
3
Palo Alto Veterans Institute of Research, Palo Alto, CA, USA.
4
Division of Pediatric Surgery, Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
5
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
6
Division of Biological Sciences, University of Montana, Missoula, MT, USA.
7
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA. pbollyky@stanford.edu.

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-β (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.

PMID:
30923196
DOI:
10.1126/science.aat9691

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center