Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS

2013 ◽  
Vol 19 (9) ◽  
pp. 1161-1165 ◽  
Author(s):  
Stefan Bittner ◽  
Tobias Ruck ◽  
Michael K Schuhmann ◽  
Alexander M Herrmann ◽  
Hamid Moha ou Maati ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes

2012 ◽  
Vol 12 (11) ◽  
pp. 762-773 ◽  
Author(s):  
Jean-Philippe Girard ◽  
Christine Moussion ◽  
Reinhold Förster
Keyword(s):  
Lymph Nodes ◽  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

Immune cell trafficking in uterus and early life is dominated by the mucosal addressin MAdCAM-1 in humans

2001 ◽  
Vol 121 (4) ◽  
pp. 853-864 ◽  
Author(s):  
Marko Salmi ◽  
Kalle Alanen ◽  
Seija Grenman ◽  
Michael Briskin ◽  
Eugene C. Butcher ◽  
...  
Keyword(s):  
Early Life ◽  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

scholarly journals Immunotherapy in CNS cancers: the role of immune cell trafficking

2018 ◽  
Vol 21 (1) ◽  
pp. 37-46 ◽  
Author(s):  
Nivedita M Ratnam ◽  
Mark R Gilbert ◽  
Amber J Giles
Keyword(s):  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

scholarly journals The molecular cues regulating immune cell trafficking

2017 ◽  
Vol 93 (4) ◽  
pp. 183-195 ◽  
Author(s):  
Akira TAKEDA ◽  
Naoko SASAKI ◽  
Masayuki MIYASAKA
Keyword(s):  
Immune Cell ◽  
Cell Trafficking ◽  
Immune Cell Trafficking

scholarly journals Human Cytomegalovirus UL111A and US27 Gene Products Enhance the CXCL12/CXCR4 Signaling Axis via Distinct Mechanisms

2017 ◽  
Vol 92 (5) ◽  
Author(s):  
Carolyn C. Tu ◽  
Kathleen L. Arnolds ◽  
Christine M. O'Connor ◽  
Juliet V. Spencer
Keyword(s):  
Human Cytomegalovirus ◽  
Chemokine Receptor ◽  
Immune Cell ◽  
Interleukin 10 ◽  
Calcium Flux ◽  
Host Immune System ◽  
Cell Trafficking ◽  
Immune Cell Trafficking ◽  
Cxcr4 Signaling ◽  
Infected Cells

ABSTRACTHuman cytomegalovirus (HCMV) is a prevalent pathogen that establishes lifelong infection in the host. Virus persistence is aided by extensive manipulation of the host immune system, particularly cytokine and chemokine signaling pathways. The HCMV UL111A gene encodes cmvIL-10, an ortholog of human interleukin-10 that has many immunomodulatory effects. We found that cmvIL-10 increased signaling outcomes from human CXCR4, a chemokine receptor with essential roles in hematopoiesis and immune cell trafficking, in response to its natural ligand CXCL12. Calcium flux and chemotaxis to CXCL12 were significantly greater in the presence of cmvIL-10 in monocytes, epithelial cells, and fibroblasts that express CXCR4. cmvIL-10 effects on CXCL12/CXCR4 signaling required the IL-10 receptor and Stat3 activation. Heightened signaling occurred both in HCMV-infected cells and in uninfected bystander cells, suggesting that cmvIL-10 may broadly influence chemokine networks by paracrine signaling during infection. Moreover, CXCL12/CXCR4 signaling was amplified in HCMV-infected cells compared to mock-infected cells even in the absence of cmvIL-10. Enhanced CXCL12/CXCR4 outcomes were associated with expression of the virally encoded chemokine receptor US27, and CXCL12/CXCR4 activation was reduced in cells infected with a deletion mutant lacking US27 (TB40/E-mCherry-US27Δ). US27 effects were Stat3 independent but required close proximity to CXCR4 in cell membranes of either HCMV-infected or US27-transfected cells. Thus, HCMV encodes two proteins, cmvIL-10 and US27, that exhibit distinct mechanisms for enhancing CXCR4 signaling. Either individually or in combination, cmvIL-10 and US27 may enable HCMV to exquisitely manipulate CXCR4 signaling to alter host immune responses and modify cell trafficking patterns during infection.IMPORTANCEThe human chemokine system plays a central role in host defense, as evidenced by the many strategies devised by viruses for manipulating it. Human cytomegalovirus (HCMV) is widespread in the human population, but infection rarely causes disease except in immunocompromised hosts. We found that two different HCMV proteins, cmvIL-10 and US27, act through distinct mechanisms to upregulate the signaling activity of a cellular chemokine receptor, CXCR4. cmvIL-10 is a secreted viral cytokine that affects CXCR4 signaling in both infected and uninfected cells, while US27 is a component of the virus particle and impacts CXCR4 activity only in infected cells. Both cmvIL-10 and US27 promote increased intracellular calcium signaling and cell migration in response to chemokine CXCL12 binding to CXCR4. Our results demonstrate that HCMV exerts fine control over the CXCL12/CXCR4 pathway, which could lead to enhanced virus dissemination, altered immune cell trafficking, and serious health implications for HCMV patients.

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