title: Dichotomy between Lactobacillus rhamnosus and Klebsiella pneumoniae on dendritic cell phenotype and function.
abstract: The reaction of the intestinal immune system to intestinal bacteria shows striking differences between various bacterial strains. Whereas Klebsiella pneumoniae induces a fierce proinflammatory reaction, the probiotic strain Lactobacillus rhamnosus has clear anti-inflammatory effect in gastrointestinal disease and allergy. The molecular basis for this dichotomy is poorly understood but is likely to involve different modulation of antigen-presenting dendritic cells (DC) by L. rhamnosus and K. pneumoniae. Hence we evaluated phenotypic and functional characteristics of DC matured in the presence of L. rhamnosus and K. pneumoniae. Monocyte-derived immature DC were cultured in the presence of live bacteria to obtain mature DC. Both micro-organisms induced maturation of immature DC as shown by CD83 and CD86 expression, but receptors involved in activation of Th1 cells were expressed predominantly on DC exposed to K. pneumoniae. In contrast to K. pneumoniae, maturation with L. rhamnosus resulted in lower TNF-alpha, IL-6, and IL-8 production by immature DC and lower IL-12 and IL-18 production by mature DC. Moreover, L. rhamnosus led to the development of T cells without a typical Th phenotype whereas K. pneumoniae induced a Th1 immune response, dependent mainly on IL-12 production. Thus our results strongly support the concept that differential modulation of DC explains the differences in the immune response to various bacterial strains and indicates that K. pneumoniae induces Th1 immune responses via DC.
authors.affiliation: Academic Medical Center, Department of Experimental Internal Medicine, PO Box 22700, 1100 DE Amsterdam, The Netherlands. h.braat@amc.uva.nl
authors.forename: Henri
authors.initials: H
authors.lastname: Braat
authors.forename: Esther C
authors.initials: EC
authors.lastname: de Jong
authors.forename: Jan M H
authors.initials: JM
authors.lastname: van den Brande
authors.forename: Martien L
authors.initials: ML
authors.lastname: Kapsenberg
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.forename: Eric A F
authors.initials: EA
authors.lastname: van Tol
authors.forename: Sander J H
authors.initials: SJ
authors.lastname: van Deventer
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000096:biosynthesis; D051940:B7-2 Antigen; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007249:Inflammation; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D007711:Klebsiella pneumoniae / Q000378:metabolism*; D007778:Lactobacillus / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000382:microbiology; D010641:Phenotype; D021122:Protein Subunits / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D051940:B7-2 Antigen; D016207:Cytokines; D007136:Immunoglobulins; D018664:Interleukin-12; D020382:Interleukin-18; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D000097802:CD83 Antigen; C419393:CD1a antigen; C497964:CD86 protein, human