Ly-6G(+)CCR2(-) myeloid cells rather than Ly-6C(high)CCR2(+) monocytes are required for the control of bacterial infection in the central nervous system

Mildner, Alexander and Djukic, Marija and Garbe, David and Wellmer, Andreas and Kuziel, William A. and Mack, Matthias and Nau, Roland and Prinz, Marco (2008) Ly-6G(+)CCR2(-) myeloid cells rather than Ly-6C(high)CCR2(+) monocytes are required for the control of bacterial infection in the central nervous system. JOURNAL OF IMMUNOLOGY, 181 (4). pp. 2713-2722. ISSN 0022-1767,

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Abstract

Myeloid cell recruitment is a characteristic feature of bacterial meningitis. However, the cellular mechanisms important for the control of Streptococcus pneumoniae infection remain largely undefined. Previous pharmacological or genetic studies broadly depleted many myeloid cell types within the meninges, which did not allow defining the function of specific myeloid subsets. Herein we show that besides CD11b(+)Ly-6G(+)CCR2(-) granulocytes, also CD11b(+)Ly-6C(high)CCR2(+) but not Ly-6C(low)CCR2(-) monocytes were recruited in high numbers to the brain as early as 12 h after bacterial challenge. Surprisingly, CD11b(+)Ly-6C(high)CCR2(+) inflammatory monacytes modulated local CXCL2 and IL-1 beta production within the meninges but did not provide protection against bacterial infection. Consistent with these results, CCR2 deficiency strongly impaired monocyte recruitment to the infected brains but was redundant for disease pathogenesis. In contrast, specific depletion of polymorphonuclear granulocytes caused elevated local bacterial titer within the brains, led to an aggravated clinical course, and enhanced mortality. These findings demonstrate that Ly-6C(high)CCR2(+) inflammatory monocytes play a redundant role for the host defense during bacterial meningitis and that predominantly CD11b(+)Ly-6G(+)CCR2(-) myeloid cells are involved in the restriction of the extracellular bacteria.

Item Type: Article
Uncontrolled Keywords: EXPERIMENTAL PNEUMOCOCCAL MENINGITIS; CHEMOKINE RECEPTOR 2; NECROSIS-FACTOR-ALPHA; DICHLOROMETHYLENE DIPHOSPHONATE; HOST-DEFENSE; BONE-MARROW; IN-VIVO; NEUTROPHIL; MACROPHAGES; CCR2;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Abteilung für Nephrologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Oct 2020 12:43
Last Modified: 26 Oct 2020 12:43
URI: https://pred.uni-regensburg.de/id/eprint/30478

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