Santus William, Barresi Simona, Mingozzi Francesca, Broggi Achille, Orlandi Ivan, Stamerra Giulia, Vai Marina, Martorana Alessandra M, Polissi Alessandra, Köhler Julia R, Liu Ningning, Zanoni Ivan, Granucci Francesca
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.
Harvard Medical School and Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA.
Sci Immunol. 2017 Sep 22;2(15). doi: 10.1126/sciimmunol.aan2725.
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 skin infections: the protective containment (abscess) and the elimination (expulsion) phases. During the early containment phase, transforming growth factor- (TGF-) induces the deposit of collagen around newly recruited polymorphonuclear cells to prevent microbial spreading. During the elimination phase, interferon- (IFN-) blocks differentiation of fibroblasts into myofibroblasts by antagonizing TGF- signaling. IFN- 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 and is a protective response to minimize tissue damage and optimize pathogen elimination.
活化T细胞核因子（NFAT）在模式识别受体下游的固有免疫细胞中被激活，但与适应性免疫相比，人们对NFAT在固有免疫中的功能了解甚少。我们发现，NFAT的早期激活平衡了对皮肤感染固有反应的两个主要阶段：保护性遏制（脓肿）阶段和清除（排出）阶段。在早期遏制阶段，转化生长因子-β（TGF-β）诱导新招募的多形核细胞周围胶原蛋白的沉积，以防止微生物扩散。在清除阶段，干扰素-γ（IFN-γ）通过拮抗TGF-β信号传导来阻断成纤维细胞向肌成纤维细胞的分化。IFN-γ还诱导纤溶酶的形成，进而促进脓肿包膜的消化和皮肤溃疡以排出微生物。NFAT控制固有IFN-γ的产生和微生物的排出。固有免疫和纤溶系统之间的这种相互作用在感染期间也会发生，并且是一种保护性反应，可将组织损伤降至最低并优化病原体清除。
