Type I interferon governs immunometabolic checkpoints that coordinate inflammation during Staphylococcal infection.
Cell Rep
; 43(8): 114607, 2024 Aug 27.
Article
in En
| MEDLINE
| ID: mdl-39126652
ABSTRACT
Macrophage metabolic plasticity is central to inflammatory programming, yet mechanisms of coordinating metabolic and inflammatory programs during infection are poorly defined. Here, we show that type I interferon (IFN) temporally guides metabolic control of inflammation during methicillin-resistant Staphylococcus aureus (MRSA) infection. We find that staggered Toll-like receptor and type I IFN signaling in macrophages permit a transient energetic state of combined oxidative phosphorylation (OXPHOS) and aerobic glycolysis followed by inducible nitric oxide synthase (iNOS)-mediated OXPHOS disruption. This disruption promotes type I IFN, suppressing other pro-inflammatory cytokines, notably interleukin-1ß. Upon infection, iNOS expression peaks at 24 h, followed by lactate-driven Nos2 repression via histone lactylation. Type I IFN pre-conditioning prolongs infection-induced iNOS expression, amplifying type I IFN. Cutaneous MRSA infection in mice constitutively expressing epidermal type I IFN results in elevated iNOS levels, impaired wound healing, vasculopathy, and lung infection. Thus, kinetically regulated type I IFN signaling coordinates immunometabolic checkpoints that control infection-induced inflammation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Staphylococcal Infections
/
Signal Transduction
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Interferon Type I
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Nitric Oxide Synthase Type II
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Methicillin-Resistant Staphylococcus aureus
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Inflammation
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Macrophages
Limits:
Animals
Language:
En
Journal:
Cell Rep
/
Cell reports
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: