title: Outer membrane protein A of Acinetobacter baumannii induces differentiation of CD4+ T cells toward a Th1 polarizing phenotype through the activation of dendritic cells.
abstract: Acinetobacter baumannii is an increasing hospital-acquired pathogen that causes a various type of infections, but little is known about the protective immune response to this microorganism. Outer membrane protein A of A. baumannii (AbOmpA) is a major porin protein and plays an important role in pathogenesis. We analyzed interaction between AbOmpA and dendritic cells (DCs) to characterize the role of this protein in promoting innate and adaptive immune responses. AbOmpA functionally activates bone marrow-derived DCs by augmenting expression of the surface markers, CD40, CD54, B7 family (CD80 and CD86) and major histocompatibility complex class I and II. AbOmpA induces production of Th1-promoting interleukin-12 from DCs and augments the syngeneic and allogeneic immunostimulatory capacity of DCs. AbOmpA stimulates production of interferon-gamma from T cells in mixed lymphocyte reactions, which suggesting Th1-polarizing capacity. CD4(+) T cells stimulated by AbOmpA-stimulated DCs show a Th1-polarizing cytokine profile. The expression of surface markers on DCs is mediated by both mitogen-activated protein kinases and NF-kappaB pathways. Our findings suggest that AbOmpA induces maturation of DCs and drives Th1 polarization, which are important properties for determining the nature of immune response against A. baumannii.
authors.affiliation: Department of Pharmacy, Pusan National University College of Pharmacy, Busan 609-735, South Korea.
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Je Chul
authors.initials: JC
authors.lastname: Lee
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Seong
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D040981:Acinetobacter baumannii / Q000276:immunology*; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D008074:Lipoproteins; D016328:NF-kappa B; C094096:OmlA protein, bacteria; D018664:Interleukin-12; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases