Nuclear factor of activated T cells (NFAT) is activated in innate immune cells downstream of pattern recognition receptors, but little is known about NFAT's functions in innate immunity compared with adaptive immunity. We show that early activation of NFAT balances the two major phases of the innate response to Candida albicans skin infections: the protective containment (abscess) and the elimination (expulsion) phases. During the early containment phase, transforming growth factor-β (TGF-β) induces the deposit of collagen around newly recruited polymorphonuclear cells to prevent microbial spreading. During the elimination phase, interferon-γ (IFN-γ) blocks differentiation of fibroblasts into myofibroblasts by antagonizing TGF-β signaling. IFN-γ also induces the formation of plasmin that, in turn, promotes abscess capsule digestion and skin ulceration for microbial discharge. NFAT controls innate IFN-γ production and microbial expulsion. This cross-talk between the innate immune and the fibrinolytic systems also occurs during infection with Staphylococcus aureus and is a protective response to minimize tissue damage and optimize pathogen elimination.
Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems / W. Santus, S. Barresi, F. Mingozzi, A. Broggi, I. Orlandi, G. Stamerra, M. Vai, A.M. Martorana, A. Polissi, J.R. Köhler, N. Liu, I. Zanoni, F. Granucci. - In: SCIENCE IMMUNOLOGY. - ISSN 2470-9468. - 2:15(2017 Sep 22). [10.1126/sciimmunol.aan2725]
Skin infections are eliminated by cooperation of the fibrinolytic and innate immune systems
A.M. Martorana;A. Polissi;
2017
Abstract
Nuclear factor of activated T cells (NFAT) is activated in innate immune cells downstream of pattern recognition receptors, but little is known about NFAT's functions in innate immunity compared with adaptive immunity. We show that early activation of NFAT balances the two major phases of the innate response to Candida albicans skin infections: the protective containment (abscess) and the elimination (expulsion) phases. During the early containment phase, transforming growth factor-β (TGF-β) induces the deposit of collagen around newly recruited polymorphonuclear cells to prevent microbial spreading. During the elimination phase, interferon-γ (IFN-γ) blocks differentiation of fibroblasts into myofibroblasts by antagonizing TGF-β signaling. IFN-γ also induces the formation of plasmin that, in turn, promotes abscess capsule digestion and skin ulceration for microbial discharge. NFAT controls innate IFN-γ production and microbial expulsion. This cross-talk between the innate immune and the fibrinolytic systems also occurs during infection with Staphylococcus aureus and is a protective response to minimize tissue damage and optimize pathogen elimination.File | Dimensione | Formato | |
---|---|---|---|
Barresi_2017_FG_iz.pdf
accesso riservato
Tipologia:
Pre-print (manoscritto inviato all'editore)
Dimensione
624.11 kB
Formato
Adobe PDF
|
624.11 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.