title: Human parechovirus and enterovirus initiate distinct CNS innate immune responses: Pathogenic and diagnostic implications.
abstract: Human parechovirus (HPeV) and enterovirus (EV) cause a range of human diseases including serious CNS infections. Little is known regarding the immune response to HPeV meningitis compared to EV meningitis or how the immune response to HPeV reflects its pathogenesis.
  
  
  
  To characterize the innate immune response to HPeV CNS infection in order to increase our understanding of HPeV pathogenesis and possibly help identify HPeV in the clinical setting.
  
  
  
  CSF samples from 13 patients with HPeV meningitis, 7 patients with EV meningitis, and 11 patients negative for CNS infections were analyzed for chemokines/cytokines using multiplex ELISA assays.
  
  
  
  CSF levels of the majority of cytokines/chemokines analyzed were significantly higher in patients with EV meningitis (EV group) compared to patients with HPeV meningitis (HPeV group) and controls. In the HPeV group, a small number of cytokine/chemokine levels were higher than controls; however, these levels were either significantly lower or not significantly different compared to the EV group. IL-6 levels were lower in HPeV than in both EV and controls.
  
  
  
  The immune response to HPeV CNS infection differs from that of EV. Distinct patterns of cytokine/chemokine expression in HPeV infections suggest HPeV-mediated modulation of the immune response. HPeV disrupts the interferon cascade and seems to interfere with early inflammatory signaling. Although HPeV elicits a predominantly muted immune reaction, a partial, general infectious-type cytokine/chemokine response does occur. Beyond providing insight into HPeV pathogenesis, the identified cytokine/chemokine profile may aid in early detection of HPeV infection.
authors.affiliation: Thomas Jefferson University Hospital, Pathology, Philadelphia, PA, United States.
authors.forename: Danielle
authors.initials: D
authors.lastname: Fortuna
authors.affiliation: Children's Hospital of Philadelphia, Pathology and Laboratory Medicine, Philadelphia, PA, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Cárdenas
authors.affiliation: Children's Hospital of Philadelphia, Pathology and Laboratory Medicine, Philadelphia, PA, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Erin H
authors.initials: EH
authors.lastname: Graf
authors.affiliation: Thomas Jefferson University Hospital, Neurosurgery, Philadelphia, PA, United States.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Harshyne
authors.affiliation: Thomas Jefferson University Hospital, Neurosurgery, Philadelphia, PA, United States; Thomas Jefferson University Hospital, Cancer Biology, Philadelphia, PA, United States.
authors.forename: D Craig
authors.initials: DC
authors.lastname: Hooper
authors.affiliation: Thomas Jefferson University Hospital, Cancer Biology, Philadelphia, PA, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Prosniak
authors.affiliation: Thomas Jefferson University Hospital, Pathology, Philadelphia, PA, United States.
authors.forename: John
authors.initials: J
authors.lastname: Shields
authors.affiliation: Thomas Jefferson University Hospital, Pathology, Philadelphia, PA, United States. Electronic address: mark.curtis@jefferson.edu.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Curtis
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000134:cerebrospinal fluid; D004770:Enterovirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008582:Meningitis, Aseptic / Q000276:immunology* / Q000821:virology*; D030061:Parechovirus / Q000276:immunology*; D012189:Retrospective Studies
chemical_list: D016207:Cytokines