TY - JOUR
T1 - Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection
AU - Sweere, Johanna M.
AU - Van Belleghem, Jonas D.
AU - Ishak, Heather
AU - Bach, Michelle S.
AU - Popescu, Medeea
AU - Sunkari, Vivekananda
AU - Kaber, Gernot
AU - Manasherob, Robert
AU - Suh, Gina A.
AU - Cao, Xiou
AU - de Vries, Christiaan R.
AU - Lam, Dung N.
AU - Marshall, Payton L.
AU - Birukova, Maria
AU - Katznelson, Ethan
AU - Lazzareschi, Daniel V.
AU - Balaji, Swathi
AU - Keswani, Sundeep G.
AU - Hawn, Thomas R.
AU - Secor, Patrick R.
AU - Bollyky, Paul L.
N1 - Publisher Copyright:
© The Authors, some rights reserved.
PY - 2019/3/29
Y1 - 2019/3/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85064138980&partnerID=8YFLogxK
U2 - 10.1126/science.aat9691
DO - 10.1126/science.aat9691
M3 - Article
C2 - 30923196
AN - SCOPUS:85064138980
SN - 0036-8075
VL - 363
JO - Science
JF - Science
IS - 6434
M1 - eaat9691
ER -