The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity

Nature Medicine

Volumn 21, Issue 12, 2015, Pages 1464-1472

  Miner, Jonathan J ^a   Daniels, Brian P ^a   Shrestha, Bimmi ^a   Proenca Modena, Jose L ^a,b   Lew, Erin D ^c   Lazear, Helen M ^a,d   Gorman, Matthew J ^a   Lemke, Greg ^c   Klein, Robyn S ^a   Diamond, Michael S ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CAMPINAS   (Brazil)

^c SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^d UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AXL RECEPTOR; BETA INTERFERON; CLAUDIN 5; GAMMA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 13; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 3; INTERLEUKIN 6; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MERTK RECEPTOR; PROTEIN TYROSINE KINASE; PROTEIN ZO1; RANTES; TUMOR NECROSIS FACTOR ALPHA; TYRO3 RECEPTOR; UNCLASSIFIED DRUG; AXL RECEPTOR TYROSINE KINASE; CHEMOKINE; MERTK PROTEIN, MOUSE; ONCOPROTEIN; PROTECTIVE AGENT; TYRO3 PROTEIN, MOUSE;

ADAPTIVE IMMUNITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY RESPONSE; ANTIGEN SPECIFICITY; ARTICLE; ASTROCYTE; B LYMPHOCYTE; BLOOD BRAIN BARRIER; BRAIN CAPILLARY ENDOTHELIAL CELL; BRAIN CORTEX; BRAIN INFECTION; BRAIN STEM; CALIFORNIA ENCEPHALITIS; CALIFORNIA ENCEPHALITIS VIRUS; CAPILLARY ENDOTHELIAL CELL; CD8+ T LYMPHOCYTE; CELL JUNCTION; CELLULAR IMMUNITY; CEREBELLUM; CONTROLLED STUDY; CROSS PRESENTATION; CYTOKINE PRODUCTION; ENDOTHELIUM CELL; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NEUROPROTECTION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; SUBCORTEX; VERO CELL LINE; VIRUS ENTRY; VIRUS LOAD; VIRUS REPLICATION; WEST NILE FEVER; WEST NILE VIRUS; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; C57BL MOUSE; DEFICIENCY; ENZYMOLOGY; KNOCKOUT MOUSE; LA CROSSE VIRUS; METABOLISM; MICROVASCULATURE; PATHOLOGY; PERMEABILITY; PHYSIOLOGY; RADIATION TOLERANCE; SIGNAL TRANSDUCTION; SURVIVAL ANALYSIS; VIROLOGY;

ADAPTIVE IMMUNITY; ANIMALS; ASTROCYTES; BLOOD-BRAIN BARRIER; CHEMOKINES; ENCEPHALITIS, CALIFORNIA; ENDOTHELIAL CELLS; INTERFERON-BETA; LA CROSSE VIRUS; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROVESSELS; PERMEABILITY; PROTECTIVE AGENTS; PROTO-ONCOGENE PROTEINS; RADIATION TOLERANCE; RECEPTOR PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION; SURVIVAL ANALYSIS; VIRAL LOAD; WEST NILE FEVER; WEST NILE VIRUS;

EID: 84946956225     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.3974     Document Type: Article

References (50)

1. Lemke, G. Biology of the TAM receptors. Cold Spring Harb. Perspect. Biol. 5, a009076 (2013).
2. Cosemans, J.M.E.M. et al. Potentiating role of Gas6 and Tyro3, Axl and Mer (TAM) receptors in human and murine platelet activation and thrombus stabilization. J. Thromb. Haemost. 8, 1797-1808 (2010).
3. Prieto, A.L., Weber, J.L. & Lai, C. Expression of the receptor protein-tyrosine kinases Tyro3, Axl and Mer in the developing rat central nervous system. J. Comp. Neurol. 425, 295-314 (2000).
4. Lew, E.D. et al. Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities. eLife 3, e03385 (2014).
5. Caraux, A. et al. Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases. Nat. Immunol. 7, 747-754 (2006).
6. Paolino, M. et al. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature 507, 508-512 (2014).
7. Holland, S.J. et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res. 70, 1544-1554 (2010).
8. Holland, S.J. et al. Multiple roles for the receptor tyrosine kinase Axl in tumor formation. Cancer Res. 65, 9294-9303 (2005).
9. Fraineau, S. et al. The vitamin K-dependent anticoagulant factor, protein S, inhibits multiple VEGF-A-induced angiogenesis events in a Mer- and SHP2-dependent manner. Blood 120, 5073-5083 (2012).
10. Angelillo-Scherrer, A. et al. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J. Clin. Invest. 115, 237-246 (2005).
11. Rothlin, C.V., Ghosh, S., Zuniga, E.I., Oldstone, M.B.A. & Lemke, G. TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 131, 1124-1136 (2007).
12. Prasad, D. et al. TAM receptor function in the retinal pigment epithelium. Mol. Cell. Neurosci. 33, 96-108 (2006).
13. Scott, R.S. et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411, 207-211 (2001).
14. Zagórska, A., Traves, P.G., Lew, E.D., Dransfield, I. & Lemke, G. Diversification of TAM receptor tyrosine kinase function. Nat. Immunol. 15, 920-928 (2014).
15. Sheridan, C. First Axl inhibitor enters clinical trials. Nat. Biotechnol. 31, 775-776 (2013).
16. Graham, D.K., DeRyckere, D., Davies, K.D. & Earp, H.S. The TAM family: phosphatidylserine-sensing receptor tyrosine kinases gone awry in cancer. Nat. Rev. Cancer 14, 769-785 (2014).
17. van den Brand, B.T. et al. Therapeutic efficacy of Tyro3, Axl and Mer tyrosine kinase agonists in collagen-induced arthritis. Arthritis Rheum. 65, 671-680 (2013).
18. Meertens, L. et al. The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry. Cell Host Microbe 12, 544-557 (2012).
19. Bhattacharyya, S. et al. Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors. Cell Host Microbe 14, 136-147 (2013).
20. Shibata, T. et al. Axl receptor blockade ameliorates pulmonary pathology resulting from primary viral infection and viral exacerbation of asthma. J. Immunol. 192, 3569-3581 (2014).
21. Subramanian, M. et al. An AXL-LRP-1-RANBP9 complex mediates DC efferocytosis and antigen cross-presentation in vivo. J. Clin. Invest. 124, 1296-1308 (2014).
22. Daniels, B.P. et al. Viral pathogen-associated molecular patterns regulate blood-brain barrier integrity via competing innate cytokine signals. MBio 5, e01476-14 (2014).
23. McJunkin, J.E. et al. La Crosse encephalitis in children. N. Engl. J. Med. 344, 801-807 (2001).
24. Wang, T. et al. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat. Med. 10, 1366-1373 (2004).
25. Zhu, D. et al. Protein S controls hypoxic-ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine-1-phosphate receptor. Blood 115, 4963-4972 (2010).
26. Chung, W.-S. et al. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 504, 394-400 (2013).
27. Brinton, M.A. Replication cycle and molecular biology of the West Nile virus. Viruses 6, 13-53 (2013).
28. Lazear, H.M. et al. Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier. Sci. Transl. Med. 7, 284ra59 (2015).
29. Sheehan, K.C. et al. Blocking monoclonal antibodies specific for mouse IFN-α/β receptor subunit 1 (Ifnar-1) from mice immunized by in vivo hydrodynamic transfection. J. Interferon Cytokine Res. 26, 804-819 (2006).
30. Etienne-Manneville, S. & Hall, A. Rho GTPases in cell biology. Nature 420, 629-635 (2002).
31. Mahajan, N.P. & Earp, H.S. An SH2 domain-dependent, phosphotyrosine-independent interaction between Vav1 and the Mer receptor tyrosine kinase: a mechanism for localizaing guanine nucleotide-exchange factor action. J. Biol. Chem. 278, 42596-42603 (2003).
32. Gautier, E.L. et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat. Immunol. 13, 1118-1128 (2012).
33. Ji, R. et al. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation. J. Immunol. 191, 6165-6177 (2013).
34. Tibrewal, N. et al. Autophosphorylation docking site Tyr867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-κB transcriptional activation. J. Biol. Chem. 283, 3618-3627 (2008).
35. + T cells responding to lethal West Nile virus infection. Eur. J. Immunol. 37, 1855-1863 (2007).
36. + T cells in control of West Nile virus infection. J. Virol. 78, 8312-8321 (2004).
37. Purtha, W.E. et al. Antigen-specific cytotoxic Tlymphocytes protect against lethal West Nile virus encephalitis. Eur. J. Immunol. 37, 1845-1854 (2007).
38. Li, Q., Lu, Q., Lu, H., Tian, S. & Lu, Q. Systemic autoimmunity in TAM triple-knockout mice causes inflammatory brain damage and cell death. PLoS ONE 8, e64812 (2013).
39. Burstyn-Cohen, T., Heeb, M.J. & Lemke, G. Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis. J. Clin. Invest. 119, 2942-2953 (2009).
40. Verma, A., Warner, S.L., Vankayalapati, H., Bearss, D.J. & Sharma, S. Targeting Axl and Mer kinases in cancer. Mol. Cancer Ther. 10, 1763-1773 (2011).
41. Suárez, R.M. et al. Inhibitors of the TAM subfamily of tyrosine kinases: synthesis and biological evaluation. Eur. J. Med. Chem. 61, 2-25 (2013).
42. Lu, Q. & Lemke, G. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro3 family. Science 293, 306-311 (2001).
43. Diamond, M.S., Shrestha, B., Marri, A., Mahan, D. & Engle, M. B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus. J. Virol. 77, 2578-2586 (2003).
44. Samuel, M.A. et al. PKR and RNase L contribute to protection against lethal West Nile virus infection by controlling early viral spread in the periphery and replication in neurons. J. Virol. 80, 7009-7019 (2006).
45. Thackray, L.B. et al. Critical role for interferon regulatory factor 3 (IRF-3) and IRF-7 in type I interferon-mediated control of murine norovirus replication. J. Virol. 86, 13515-13523 (2012).
46. Mehlhop, E. & Diamond, M.S. Protective immune responses against West Nile virus are primed by distinct complement activation pathways. J. Exp. Med. 203, 1371-1381 (2006).
47. Diamond, M.S. et al. A critical role for induced IgM in the protection against West Nile virus infection. J. Exp. Med. 198, 1853-1862 (2003).
48. + T cell-dependent clearance of West Nile virus from the central nervous system. J. Virol. 87, 11401-11415 (2013).
49. Thackray, L.B. et al. Interferon regulatory factor 5 (IRF5)-dependent immune responses in the draining lymph node protect against West Nile virus infection. J. Virol. 88, 11007-11021 (2014).
50. Howell, G.R. et al. Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma. J. Clin. Invest. 122, 1246-1261 (2012).