title: Bacterial reprogramming of PBMCs impairs monocyte phagocytosis and modulates adaptive T cell responses.
abstract: Septic diseases are characterized by an initial systemic, proinflammatory phase, followed by a period of anti-inflammation. In the context of the latter, monocytes have been described to display altered functions, including reduced TNF secretion and T cell-stimulating capacities in response to recall antigens. This hyporesponsiveness is supposed to be detrimental for coping with secondary infections. We here characterize bacterially reprogrammed PBMC-derived monocytes with special focus on their phagocytic activity. Hence, we have implemented a surrogate model of the early, postinflammatory period by exposing PBMCs to Escherichia coli on d0 and rechallenging them with bacteria on d2. This induced the emergence of a distinct monocytic phenotype with profound phagocytic impairments but a preserved ability for naïve T cell stimulation. The compromising effects on phagocytosis required the presence of bacteria and were not mimicked by TLR4 ligation or exposure to isolated cytokines alone. Moreover, the impairments were specific for the engulfment of bacteria and were coupled to a selective down-regulation of FcγR and SR expression. Intriguingly, this monocytic phenotype contributed to the stimulation of a T(H)17-polarized adaptive immune response in the context of secondary infection. Our findings extend the current knowledge of monocytic reprogramming and identify the phagocytic capacity of monocytes as a putative sepsis biomarker.
authors.affiliation: Department of Neonatology, University Children’s Hospital, Tuebingen, Germany. maya.andre@med.uni-tuebingen.de
authors.forename: Maya C
authors.initials: MC
authors.lastname: André
authors.forename: Christian
authors.initials: C
authors.lastname: Gille
authors.forename: Philip
authors.initials: P
authors.lastname: Glemser
authors.forename: Jeanette
authors.initials: J
authors.lastname: Woiterski
authors.forename: Hsin-Yun
authors.initials: HY
authors.lastname: Hsu
authors.forename: Baerbel
authors.initials: B
authors.lastname: Spring
authors.forename: Hildegard
authors.initials: H
authors.lastname: Keppeler
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Christian F
authors.initials: CF
authors.lastname: Poets
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.forename: Thorsten W
authors.initials: TW
authors.lastname: Orlikowsky
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology* / Q000378:metabolism; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; C489017:FCGR1A protein, human; D017452:Receptors, IgG; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha