Bacterial reprogramming of PBMCs impairs monocyte phagocytosis and modulates adaptive T cell responses

Maya C. André, Christian Gille, Philip Glemser, Jeanette Woiterski, Hsin-Yun Hsu, Baerbel Spring, Hildegard Keppeler, Boris W. Kramer, Rupert Handgretinger, Christian F. Poets, Kirsten Lauber, Thorsten W. Orlikowsky

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 TH17-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.

Original languageEnglish
Pages (from-to)977-989
Number of pages13
JournalJournal of Leukocyte Biology
Volume91
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Anti-inflammatory response
  • E. coli
  • TH17
  • TLR

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