title: Meningitis Caused by Toscana Virus Is Associated with Strong Antiviral Response in the CNS and Altered Frequency of Blood Antigen-Presenting Cells.
abstract: 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.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy. stefania.varani@unibo.it.|Unit of Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, via Massarenti 9, 40138 Bologna, Italy. stefania.varani@unibo.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Varani
authors.affiliation: Unit of Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, via Massarenti 9, 40138 Bologna, Italy. francesco.gelsomino1@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gelsomino
authors.affiliation: Infectious Disease Unit, Department of Medical and Surgical Science, University of Bologna, 40138 Bologna, Italy. bartolettimichele@yahoo.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Bartoletti
authors.affiliation: Infectious Disease Unit, Department of Medical and Surgical Science, University of Bologna, 40138 Bologna, Italy. pierluigi.viale@unibo.it.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Viale
authors.affiliation: Infectious Disease Unit, G.B. Morgagni-Pierantoni Hospital, 47121 Forlì, Italy. antoniomastroianni@yahoo.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mastroianni
authors.affiliation: Infectious Disease Unit, G.B. Morgagni-Pierantoni Hospital, 47121 Forlì, Italy. elisabettabriganti@libero.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Briganti
authors.affiliation: Infectious Disease Unit, Infermi Hospital, 47923 Rimini, Italy. o.patrizia@tiscali.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ortolani
authors.affiliation: Division of Infectious Diseases, St. Maria delle Croci Hospital, 48121 Ravenna, Italy. fr.albertini@libero.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Albertini
authors.affiliation: Unit of Infectious Diseases and Hepatology, Parma University Hospital, 43126 Parma, Italy. ccalzetti@ao.pr.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Calzetti
authors.affiliation: Infectious Disease Division, Reggio Emilia Hospital, 42100 Reggio Emilia, Italy. francesca.prati2@asmn.re.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Prati
authors.affiliation: Emergency Department, Ospedale Civile St. Maria della Scaletta, 40026 Imola, Italy. p.cenni@ausl.imola.bo.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cenni
authors.affiliation: Department of Physics and Astronomy and Galvani Center for Biocomplexity, University of Bologna, 40127 Bologna, Italy.
authors.forename: Gastone
authors.initials: G
authors.lastname: Castellani
authors.affiliation: Unit of Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, via Massarenti 9, 40138 Bologna, Italy. silvia-morini@libero.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morini
authors.affiliation: Unit of Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, via Massarenti 9, 40138 Bologna, Italy. giada.rossini@unibo.it.
authors.forename: Giada
authors.initials: G
authors.lastname: Rossini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy. mariapaola.landini@unibo.it.|Unit of Microbiology, Regional Reference Centre for Microbiological Emergencies (CRREM), St. Orsola-Malpighi University Hospital, via Massarenti 9, 40138 Bologna, Italy. mariapaola.landini@unibo.it.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Landini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy. vittorio.sambri@unibo.it.|Unit of Microbiology, "AUSL della Romagna" Hub Laboratory, 47522 Pievesestina, (FC), Italy. vittorio.sambri@unibo.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sambri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002044:Bunyaviridae Infections / Q000276:immunology* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D008297:Male; D008587:Meningitis, Viral / Q000276:immunology* / Q000473:pathology*; D008875:Middle Aged; D029301:Sandfly fever Naples virus / Q000254:growth & development / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: Toscana virus; cytokines; dendritic cells; monocytes; viral meningitis