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

Journal of Leukocyte Biology

Hsin-Yun Hsu²  Kirsten Lauber–#, and⁶  Boris W. Kramer⁷  Jeanette Woiterski³  Baerbel Spring¹  Rupert Handgretinger³  Hildegard Keppeler–⁶  Christian F. Poets¹  Christian Gille¹  Maya C. André, ⁴  Philip Glemser¹  Thorsten W. Orlikowsky,⁵ 

[1] Departments of Neonatology and #Department of Radiation Oncology, Molecular Oncology, Ludwig-Maximilians-University of Munich, Germany Department of Neonatology, University Children's Hospital, Aachen, Germany;;NMI Natural and Medical Sciences Institute and Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan; #Department of Radiation Oncology, Molecular Oncology, Ludwig-Maximilians-University of Munich, Germany Pediatric Hematology and Oncology, University Children's Hospital, Tuebingen, and #Department of Radiation Oncology, Molecular Oncology, Ludwig-Maximilians-University of Munich, Germany Department of Neonatology, University Children's Hospital, Aachen, Germany;Departments of Neonatology and  Pediatric Hematology and Oncology, University Children's Hospital, Tuebingen, and #Department of Radiation Oncology, Molecular Oncology, Ludwig-Maximilians-University of Munich, Germany Department of Neonatology, University Children's Hospital, Aachen, Germany;;Departments of Neonatology and Department of Neonatology, University Children's Hospital, Aachen, Germany; #Department of Radiation Oncology, Molecular Oncology, Ludwig-Maximilians-University of Munich, Germany;–Department of Internal Medicine I, University of Tuebingen, Germany; #Department of Radiation Oncology, Molecular Oncology, Ludwig-Maximilians-University of Munich, Germany;Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands; and #Department of Radiation Oncology, Molecular Oncology, Ludwig-Maximilians-University of Munich, Germany

关键词: E. coli;    anti-inflammatory response;    TLR;    T_H17;   

DOI  :  10.1189/jlb.0911474

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 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 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.

【 授权许可】

Unknown