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DNA Sensor IFI204 Contributes to Host Defense Against Staphylococcus aureus Infection in Mice.
- Source :
-
Frontiers in immunology [Front Immunol] 2019 Mar 18; Vol. 10, pp. 474. Date of Electronic Publication: 2019 Mar 18 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Interferon-inducible protein (IFI204) (p204, the murine homolog of human IFI16) is known as a cytosolic DNA sensor to recognize DNA viruses and intracellular bacteria. However, little is known about its role during extracellular bacterial infection. Here we show that IFI204 is required for host defense against the infection of Staphylococcus aureus , an extracellular bacterial pathogen. IFI204 deficiency results in decreased survival, increased bacterial loads, severe organs damage, and decreased recruitment of neutrophils and macrophages. Production of several inflammatory cytokines/chemokines including IFN-β and KC is markedly decreased, as well as the related STING-IRF3 and NF-κB pathways are impaired. However, exogenous administration of recombinant KC or IFN-β is unable to rescue the susceptibility of IFI204-deficient mice, suggesting that other mechanisms rather than KC and IFN-β account for IFI204-mediated host defense. IFI204 deficiency leads to a defect in extracellular bacterial killing in macrophages and neutrophils, although bacterial engulf, and intracellular killing activity are normal. Moreover, the defect of bactericidal activity is mediated by decreased extracellular trap formation in the absence of IFI204. Adoptively transferred WT bone marrow cells significantly protect WT and IFI204-deficient recipients against Staphylococcus infection compared with transferred IFI204-deficient bone marrow cells. Hence, this study suggests that IFI204 is essential for the host defense against Staphylococcus infection.
- Subjects :
- Animals
Bacteremia immunology
Bacteremia microbiology
Bacterial Load
Bone Marrow Transplantation
Chemokine CXCL1 biosynthesis
Chemokine CXCL1 immunology
Chemokine CXCL1 pharmacology
Cytokines biosynthesis
Female
Interferon Regulatory Factor-3 physiology
Interferon-beta biosynthesis
Interferon-beta immunology
Interferon-beta pharmacology
Macrophages microbiology
Macrophages, Peritoneal immunology
Macrophages, Peritoneal microbiology
Male
Membrane Proteins physiology
Mice
Mice, Inbred C57BL
NF-kappa B physiology
Neutrophils immunology
Nuclear Proteins deficiency
Phosphoproteins deficiency
Pneumonia, Staphylococcal immunology
Pneumonia, Staphylococcal microbiology
Radiation Chimera
Recombinant Proteins pharmacology
Signal Transduction
Staphylococcal Infections microbiology
DNA, Bacterial immunology
Macrophages immunology
Neutrophils microbiology
Nuclear Proteins immunology
Phosphoproteins immunology
Staphylococcal Infections immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30936875
- Full Text :
- https://doi.org/10.3389/fimmu.2019.00474