Varani Stefania, Gelsomino Francesco, Bartoletti Michele, Viale Pierluigi, Mastroianni Antonio, Briganti Elisabetta, Ortolani Patrizia, Albertini Francesco, Calzetti Carlo, Prati Francesca, Cenni Patrizia, Castellani Gastone, Morini Silvia, Rossini Giada, Landini Maria Paola, Sambri Vittorio
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy.
Unit of Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, via Massarenti 9, 40138 Bologna, Italy.
Viruses. 2015 Nov 11;7(11):5831-43. doi: 10.3390/v7112909.
Toscana virus (TOSV) is a Phlebotomus-transmitted RNA virus and a frequent cause of human meningitis and meningoencephalitis in Southern Europe during the summer season. While evidence for TOSV-related central nervous system (CNS) cases is increasing, little is known about the host defenses against TOSV. We evaluated innate immune response to TOSV by analyzing frequency and activation of blood antigen-presenting cells (APCs) and cytokine levels in plasma and cerebrospinal fluid (CSF) from patients with TOSV neuroinvasive infection and controls. An altered frequency of different blood APC subsets was observed in TOSV-infected patients, with signs of monocytic deactivation. Nevertheless, a proper or even increased responsiveness of toll-like receptor 3 and 7/8 was observed in blood APCs of these patients as compared to healthy controls. Systemic levels of cytokines remained low in TOSV-infected patients, while levels of anti-inflammatory and antiviral mediators were significantly higher in CSF from TOSV-infected patients as compared to patients with other infectious and noninfectious neurological diseases. Thus, the early host response to TOSV appears effective for viral clearance, by proper response to TLR3 and TLR7/8 agonists in peripheral blood and by a strong and selective antiviral and anti-inflammatory response in the CNS.
托斯卡纳病毒（TOSV）是一种由白蛉传播的RNA病毒，是夏季南欧人类脑膜炎和脑膜脑炎的常见病因。虽然与TOSV相关的中枢神经系统（CNS）病例的证据在增加，但对宿主针对TOSV的防御机制知之甚少。我们通过分析TOSV神经侵袭性感染患者和对照组的血液抗原呈递细胞（APC）的频率和活化情况以及血浆和脑脊液（CSF）中的细胞因子水平，评估了对TOSV的先天免疫反应。在TOSV感染患者中观察到不同血液APC亚群的频率改变，伴有单核细胞失活的迹象。然而，与健康对照相比，这些患者血液中的APC中Toll样受体3和7/8的反应性适当甚至增加。TOSV感染患者的全身细胞因子水平仍然较低，而与其他感染性和非感染性神经系统疾病患者相比，TOSV感染患者脑脊液中抗炎和抗病毒介质的水平显著更高。因此，宿主对TOSV的早期反应似乎通过对外周血中TLR3和TLR7/8激动剂的适当反应以及中枢神经系统中强烈且选择性的抗病毒和抗炎反应，对病毒清除有效。
