CXCL16 Contributes to Neutrophil Recruitment to Cerebrospinal Fluid in Pneumococcal Meningitis

Woehrl, Bianca; Klein, Matthias; Rupprecht, Tobias A.; Schmetzer, Helga; Angele, Barbara; Häcker, Georg; Pfister, Hans‐Walter; Koedel, Uwe

doi:10.1086/656532

Cited by 27 publications

(18 citation statements)

References 23 publications

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“…MIP‐3α/CCL20 will stimulate the migration, homing and maturation of leucocytes, and CCL20 together with CXCL1, CXCL2, IL‐6 and IL‐8 increased more than 100‐fold in blood–brain barrier endothelial cells during Pf‐IRBC contact, which suggests its participation in cellular defence during Pf‐IRBC sequestration [60]. Astrocytes which line parenchymal blood vessels will respond in a pathogen‐specific way to infection and release MIP‐3α/CCL20 and CXCL16 [61]; both chemokines will promote Th1‐type responses by enhancing IFN‐γ and TNF‐α release, and CXCL16 may attract neutrophil granulocytes across the blood–brain barrier into the cerebrospinal fluid [62,63]. Both CCL20 and CXCL16 were elevated substantially in SM and MM infants; CCL20 correlated positively with parasite densities, and therefore CCL20 and CXCL16 should be investigated further as to what extent they contribute to the manifestation of CM.…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory and regulatory cytokines and chemokines in infants with uncomplicated and severePlasmodium falciparummalaria

Ayimba

Hegewald

Segbena

et al. 2011

Clinical and Experimental Immunology

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SummaryCytokine and chemokine levels were studied in infants (<5 years) with uncomplicated (MM) and severe malaria tropica (SM), and in Plasmodium falciparum infection-free controls (NEG). Cytokine plasma levels of interleukin (IL)-10, IL-13, IL-31 and IL-33 were strongly elevated in MM and SM compared to NEG (P < 0·0001). Inversely, plasma concentrations of IL-27 were highest in NEG infants, lower in MM cases and lowest in those with SM (P < 0·0001, NEG compared to MM and SM). The levels of the chemokines macrophage inflammatory protein (MIP3)-a/C-C ligand 20 (CCL20), monokine induced by gamma interferon (MIG)/CXCL9 and CXCL16 were enhanced in those with MM and SM (P < 0·0001 compared to NEG), and MIP3-a/CCL20 and MIG/CXCL9 were correlated positively with parasite density, while that of IL-27 were correlated negatively. The levels of 6Ckine/ CCL21 were similar in NEG, MM and SM. At 48-60 h post-anti-malaria treatment, the plasma concentrations of IL-10, IL-13, MIG/CXCL9, CXCL16 and MIP3-a/CCL20 were clearly diminished compared to before treatment, while IL-17F, IL-27, IL-31 and IL-33 remained unchanged. In summary, elevated levels of proinflammatory and regulatory cytokines and chemokines were generated in infants during and after acute malaria tropica. The proinflammatory type cytokines IL-31 and IL-33 were enhanced strongly while regulatory IL-27 was diminished in those with severe malaria. Similarly, MIP3-a/ CCL20 and CXCL16, which may promote leucocyte migration into brain parenchyma, displayed increased levels, while CCL21, which mediates immune surveillance in central nervous system tissues, remained unchanged. The observed cytokine and chemokine production profiles and their dynamics may prove useful in evaluating either the progression or the regression of malarial disease.

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Section: Discussionmentioning

confidence: 99%

Proinflammatory and regulatory cytokines and chemokines in infants with uncomplicated and severePlasmodium falciparummalaria

Ayimba

Hegewald

Segbena

et al. 2011

Clinical and Experimental Immunology

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“…CNS inflammatory diseases, such as bacterial meningitis (Woehrl et al 2010), multiple sclerosis (Larochelle et al 2011), and stroke (Perez-de-Puig et al 2015). Once adhered to the endothelium, monocytes produce reactive oxygen species (ROS), release proteases, and generate cationic proteins and other substances that damage microvessels (Granger and Senchenkova 2010).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Human Brain Microvascular Endothelial Cell Adhesion and Barrier Functions by Memantine

et al. 2017

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Vascular risk factors have been linked to cognitive decline and dementia in the elderly. Microvascular inflammation, especially of the endothelium, may contribute to the progression of neurodegenerative events in Alzheimer's disease (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is a licensed drug used for the treatment of moderate to severe AD. However, little information is available regarding its anti-inflammatory effects on the endothelium. In this study, we investigated the effects of memantine on human brain microvascular endothelial dysfunction induced by the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Our results show that memantine prevents the attachment of monocyte THP-1 cells to human brain microvascular endothelial cells (HBMVEs). An in vitro BBB model experiment displayed that memantine could rescue TNF-α-induced disruption of the in vitro BBB model. In addition, memantine also interferes with monocyte transmigration across the BBB model. Our results indicate that TNF-α significantly increased the expression of cell adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin, which was prevented by pretreatment with memantine. Mechanistically, memantine reversed activation of the transcription factor NF-κB by preventing the phosphorylation and degradation of its inhibitor IκBα. Our data is the first to describe a novel anti-inflammatory mechanism driven by the endothelial cell-mediated neuroprotective effects of memantine.

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“…Although the brain is considered to be an immune-privileged organ [ 1 , 2 ], devastating effects can occur in the brain during local inflammation, particularly in response to cerebral bacterial infection. The recruitment of immune cells from the circulation is critical for many life-threatening central nervous system (CNS) inflammatory diseases, such as bacterial meningitis [ 3 ], multiple sclerosis [ 4 ], and stroke [ 5 ]. Neutrophils mobilized from the circulation in response to signals from the CXC family of chemokines, such as keratinocyte-derived chemokine (KC, CXCL1), and macrophage inflammatory protein-2 (MIP-2, CXCL2), are considered to be the first line of defense against bacteria [ 6 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain

Zou

Ding

et al. 2016

J Neuroinflammation

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BackgroundThe complement system is becoming increasingly recognized as a key participant in many neurodegenerative diseases of the brain. Complement-deficient animals exhibit reduced neuroinflammation.MethodsIn the present study, we administered intracerebroventricularly lipopolysaccharide (LPS) to mimic local infection of the brain and investigated the role of key complement component C3 in brain vasculature endothelial activation and leukocyte recruitment. The degree of neutrophil infiltration was determined by esterase staining. Leukocyte-endothelial interactions were measured using intravital microscopy. Cerebral endothelial activation was evaluated using real-time PCR and Western blotting.ResultsNeutrophil infiltration into the brain cortex and hippocampus was significantly reduced in C3−/− mice and C3aR−/− mice but not in C6−/− mice. We detected markedly attenuated leukocyte-endothelial interactions in the brain microvasculature of C3−/− mice. Accordingly, in response to LPS administration, the brain microvasculature in these mice had decreased expression of P-selectin, E-selectin, intercellular cell adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Depletion of C3 from the circulation also caused reduction in VCAM-1 and E-selectin expression and leukocyte recruitment, suggesting that C3 in the circulation contributed to brain endothelial activation. Furthermore, C3−/− mice exhibited decreased leukocyte recruitment into the brain upon tumor necrosis factor-α (TNF-α) stimulation. C3a activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) and induced the upregulation of VCAM-1 and ICAM-1 expression in murine primary cerebral endothelial cells in vitro.ConclusionsOur study provides the first evidence that C3a plays a critical role in cerebral endothelial activation and leukocyte recruitment during inflammation in the brain.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0485-y) contains supplementary material, which is available to authorized users.

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CXCL16 Contributes to Neutrophil Recruitment to Cerebrospinal Fluid in Pneumococcal Meningitis

Cited by 27 publications

References 23 publications

Proinflammatory and regulatory cytokines and chemokines in infants with uncomplicated and severePlasmodium falciparummalaria

Proinflammatory and regulatory cytokines and chemokines in infants with uncomplicated and severePlasmodium falciparummalaria

Regulation of Human Brain Microvascular Endothelial Cell Adhesion and Barrier Functions by Memantine

Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain

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