標題: Bacterial reprogramming of PBMCs impairs monocyte phagocytosis and modulates adaptive T cell responses
作者: Andre, Maya C.
Gille, Christian
Glemser, Philip
Woiterski, Jeanette
Hsu, Hsin-Yun
Spring, Baerbel
Keppeler, Hildegard
Kramer, Boris W.
Handgretinger, Rupert
Poets, Christian F.
Lauber, Kirsten
Orlikowsky, Thorsten W.
應用化學系
Department of Applied Chemistry
關鍵字: E. coli;anti-inflammatory response;TLR;T(H)17
公開日期: 1-Jun-2012
摘要: 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 naive 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 Fc gamma R 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. J. Leukoc. Biol. 91: 977-989; 2012.
URI: http://hdl.handle.net/11536/16274
ISSN: 0741-5400
期刊: JOURNAL OF LEUKOCYTE BIOLOGY
Volume: 91
Issue: 6
結束頁: 977
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