Ly-6G+CCR2- myeloid cells rather than Ly-6ChighCCR2+ monocytes are required for the control of bacterial infection in the central nervous system.
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 monocytes modulated local CXCL2 and IL-1beta 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.
Mildner
Alexander
A
Department of Neuropathology, University of Freiburg, Freiburg, Germany.
Djukic
Marija
M
Garbe
David
D
Wellmer
Andreas
A
Kuziel
William A
WA
Mack
Matthias
M
Nau
Roland
R
Prinz
Marco
M
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016130:Immunophenotyping; D008297:Male; D008586:Meningitis, Pneumococcal / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D054390:Receptors, CCR2 / Q000096:biosynthesis / Q000172:deficiency* / Q000502:physiology
D000950:Antigens, Ly; C515335:Ccr2 protein, mouse; C494192:Ly-6C antigen, mouse; C526827:Ly6 protein, mouse; C480309:Ly6G antigen, mouse; D054390:Receptors, CCR2