title: The intestinal archaea Methanosphaera stadtmanae and Methanobrevibacter smithii activate human dendritic cells.
abstract: The methanoarchaea Methanosphaera stadtmanae and Methanobrevibacter smithii are known to be part of the indigenous human gut microbiota. Although the immunomodulatory effects of bacterial gut commensals have been studied extensively in the last decade, the impact of methanoarchaea in human's health and disease was rarely examined. Consequently, we studied and report here on the effects of M. stadtmanae and M. smithii on human immune cells. Whereas exposure to M. stadtmanae leads to substantial release of proinflammatory cytokines in monocyte-derived dendritic cells (moDCs), only weak activation was detected after incubation with M. smithii. Phagocytosis of M. stadtmanae by moDCs was demonstrated by confocal microscopy as well as transmission electronic microscopy (TEM) and shown to be crucial for cellular activation by using specific inhibitors. Both strains, albeit to different extents, initiate a maturation program in moDCs as revealed by up-regulation of the cell-surface receptors CD86 and CD197 suggesting additional activation of adaptive immune responses. Furthermore, M. stadtmanae and M. smithii were capable to alter the gene expression of antimicrobial peptides in moDCs to different extents. Taken together, our findings strongly argue that the archaeal gut inhabitants M. stadtmanae and M. smithii are specifically recognized by the human innate immune system. Moreover, both strains are capable of inducing an inflammatory cytokine response to different extents arguing that they might have diverse immunomodulatory functions. In conclusion, we propose that the impact of intestinal methanoarchaea on pathological conditions involving the gut microbiota has been underestimated until now.
authors.affiliation: Institute for General Microbiology, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Bang
authors.affiliation: Institute for General Microbiology, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Weidenbach
authors.affiliation: Division of Biophysics, Research Center Borstel, Borstel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.affiliation: Division of Innate Immunity, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research (DZL), Borstel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Heine
authors.affiliation: Institute for General Microbiology, Christian-Albrechts-University Kiel, Kiel, Germany.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Schmitz
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D017013:Methanobacteriaceae / Q000502:physiology*; D041581:Methanobrevibacter / Q000502:physiology*; D009000:Monocytes / Q000166:cytology; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D011956:Receptors, Cell Surface