title: Pathogenic hantaviruses elicit different immunoreactions in THP-1 cells and primary monocytes and induce differentiation of human monocytes to dendritic-like cells.
abstract: Hantaviruses cause two important human illnesses, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Both syndromes are believed to be immune-mediated diseases. Monocytes/macrophages are thought to be the main target cells for hantaviruses and important sources of and targets for cytokines/chemokines secretion. THP-1 cells have been used extensively as models for primary monocytes in biocompatibility research. The aim of our study was to determine if hantaviruses induce the same immunoreactions in THP-1 cells and primary monocytes/ macrophages and might therefore be suitable for immune studies of hantaviral infections. For that purpose we compared various cytokines/chemokines and their receptors in THP-1 cell line and primary monocytes/macrophages. Infected primary monocytes/macrophages induced mostly beta-chemokines and their receptors. In contrast, THP-1 cells, expressed receptors for CXC chemokines. Surprisingly, infected macrophages underwent morphological changes toward dendritic-like cells and increased expression of co-stimulatory molecules: CD40, CD80, CD83 and CD86. Our data indicate that THP-1 cells are not ideal for in vitro research of the immunopathogenesis of hantaviruses in humans. Further, our studies revealed potential roles for cytokines/chemokines in HFRS/HPS immunopathogenesis and point to intriguing possibilities for the possible differentiation of infected macrophages to dendritic-like cells.
authors.affiliation: Scientific Unit, University Hospital for Infectious Diseases "Dr. Fran Mihaljević", Zagreb, Croatia. alemka.markotic@bfm.hr
authors.forename: Alemka
authors.initials: A
authors.lastname: Markotić
authors.forename: Lisa
authors.initials: L
authors.lastname: Hensley
authors.forename: Kathleen
authors.initials: K
authors.lastname: Daddario
authors.forename: Kristin
authors.initials: K
authors.lastname: Spik
authors.forename: Kevin
authors.initials: K
authors.lastname: Anderson
authors.forename: Connie
authors.initials: C
authors.lastname: Schmaljohn
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D002454:Cell Differentiation; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology*; D006476:Orthohantavirus / Q000472:pathogenicity*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D019013:CD40 Antigens; D018925:Chemokines; D016207:Cytokines; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen