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Dendritic cell activation by sensing Mycobacterium tuberculosis-induced apoptotic neutrophils via DC-SIGN
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
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2010 (English)In: HUMAN IMMUNOLOGY, ISSN 0198-8859, Vol. 71, no 6, 535-540 p.Article in journal (Refereed) Published
Abstract [en]

Mycobacterium tuberculosis (Mtb) manipulates cells of the innate immune system to provide the bacteria with a sustainable intracellular niche. Mtb spread through aerosol carrying them deep into the lungs, where they are internalized by phagocytic cells, such as neutrophils (PMNs), dendritic cells (DCs), and macrophages. PMNs undergo accelerated apoptosis after interaction with the bacterium, and apoptotic cells are sequestered by neighboring phagocytes. Removal of aged apoptotic cells because of natural tissue turnover is described as an immunologically silent process facilitating resolution of inflammation and inhibition of DC maturation. Silencing of immune cells could be favorable for intracellular bacteria. The aim of this study was to clarify the interaction between Mtb-induced apoptotic PMNs and DCs, and evaluate whether this interaction follows the proposed anti-inflammatory pathway. In contrast to aged apoptotic cells, Mtb-induced apoptotic PMNs induced functional DC maturation. We found that the cell fraction from Mtb-induced apoptotic PMNs contained almost all stimulatory capacity, suggesting that cell-cell interaction is crucial for DC activation. Inhibitory studies showed that this cell contact-dependent activation required binding of the PMN Mac-1 (CD11b/CD18) to the DC via DC-SIGN and endocytic activity involving the alpha(v)beta(5) but did not involve the scavenger receptor CD36. Taken together, this study demonstrates that the DCs can distinguish between normal and infected apoptotic PMNs via cellular crosstalk, where the DCs can sense the presence of danger on the Mtb-infected PMNs and modulate their response accordingly.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam. , 2010. Vol. 71, no 6, 535-540 p.
Keyword [en]
Mycobacterium tuberculosis, Dendritic cell maturation, Apoptoptic cells
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-57409DOI: 10.1016/j.humimm.2010.02.022ISI: 000278426100001OAI: oai:DiVA.org:liu-57409DiVA: diva2:325499
Available from: 2010-06-18 Created: 2010-06-18 Last updated: 2010-06-18

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Hedlund, SebastianPersson, AlexanderVujic, AnaFru Che, KarlhansStendahl, OlleLarsson, Marie

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Hedlund, SebastianPersson, AlexanderVujic, AnaFru Che, KarlhansStendahl, OlleLarsson, Marie
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Department of Clinical and Experimental MedicineFaculty of Health SciencesMedical Microbiology Molecular Virology
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