Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells

Nature Medicine

Volumn 22, Issue 5, 2016, Pages 516-523

  Benakis, Corinne ^a   Brea, David ^a   Caballero, Silvia ^b,c   Faraco, Giuseppe ^a   Moore, Jamie ^a   Murphy, Michelle ^a   Sita, Giulia ^a   Racchumi, Gianfranco ^a   Ling, Lilan ^b   Pamer, Eric G ^b,c   Iadecola, Costantino ^a   Anrather, Josef ^a  

^a FEIL FAMILY BRAIN AND MIND RESEARCH INSTITUTE   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^c Weill Graduate School of Medical Sciences of Cornell University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMOXICILLIN; CLAVULANIC ACID; INTERLEUKIN 10; INTERLEUKIN 17; VANCOMYCIN; ANTIINFECTIVE AGENT; IL10 PROTEIN, MOUSE; LYMPHOCYTE ANTIGEN RECEPTOR; MESSENGER RNA; RNA 16S;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIBIOTIC THERAPY; ARTICLE; BRAIN ISCHEMIA; CELL ACTIVITY; CELL MIGRATION; CONTROLLED STUDY; DENDRITIC CELL; DYSBIOSIS; FECAL MICROBIOTA TRANSPLANTATION; HOMEOSTASIS; IMMUNE SYSTEM; INTESTINE CELL; INTESTINE FLORA; LYMPHOCYTE DIFFERENTIATION; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; MOUSE; NEUROPROTECTION; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; ANIMAL; ANIMAL BEHAVIOR; BLOOD BRAIN BARRIER; BRAIN; CEREBRAL ARTERY DISEASE; CEREBROVASCULAR ACCIDENT; DRUG EFFECTS; FLOW CYTOMETRY; GENETICS; IMMUNOHISTOCHEMISTRY; IMMUNOLOGY; INTESTINE; INTESTINE MUCOSA; LEUKOCYTE; LYMPHOCYTE; METABOLISM; MICROBIOLOGY; MUCOSAL IMMUNITY; PATHOPHYSIOLOGY; SMALL INTESTINE; T LYMPHOCYTE;

ANIMALS; ANTI-BACTERIAL AGENTS; BEHAVIOR, ANIMAL; BLOOD-BRAIN BARRIER; BRAIN; BRAIN ISCHEMIA; DENDRITIC CELLS; DYSBIOSIS; FECAL MICROBIOTA TRANSPLANTATION; FLOW CYTOMETRY; GASTROINTESTINAL MICROBIOME; IMMUNITY, MUCOSAL; IMMUNOHISTOCHEMISTRY; INFARCTION, MIDDLE CEREBRAL ARTERY; INTERLEUKIN-10; INTERLEUKIN-17; INTESTINAL MUCOSA; INTESTINE, SMALL; INTESTINES; LEUKOCYTES; LYMPHOCYTES; MICE; RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA; RNA, MESSENGER; RNA, RIBOSOMAL, 16S; STROKE; T-LYMPHOCYTES; T-LYMPHOCYTES, REGULATORY;

EID: 84961875569     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.4068     Document Type: Article

References (62)

1. Henninger, N., Kumar, R. & Fisher, M. Acute ischemic stroke therapy. Expert Rev. Cardiovasc. Ther. 8, 1389-1398 (2010).
2. Iadecola, C. & Anrather, J. The immunology of stroke: from mechanisms to translation. Nat. Med. 17, 796-808 (2011).
3. Macrez, R. et al. Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol. 10, 471-480 (2011).
4. Mazmanian, S.K., Liu, C.H., Tzianabos, A.O. & Kasper, D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107-118 (2005).
5. Prinz, I., Silva-Santos, B. & Pennington, D.J. Functional development of γδ T cells. Eur. J. Immunol. 43, 1988-1994 (2013).
6. Shichita, T. et al. Pivotal role of cerebral interleukin-17-producing γδ T cells in the delayed phase of ischemic brain injury. Nat. Med. 15, 946-950 (2009).
7. Gelderblom, M. et al. Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. Blood 120, 3793-3802 (2012).
8. Liesz, A., Hu, X., Kleinschnitz, C. & Offner, H. Functional role of regulatory lymphocytes in stroke: facts and controversies. Stroke 46, 1422-1430 (2015).
9. Liesz, A. et al. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat. Med. 15, 192-199 (2009).
10. Stubbe, T. et al. Regulatory T cells accumulate and proliferate in the ischemic hemisphere for up to 30 days after MCAO. J. Cereb. Blood Flow Metab. 33, 37-47 (2013).
11. Li, P. et al. Adoptive regulatory T cell therapy protects against cerebral ischemia. Ann. Neurol. 74, 458-471 (2013).
12. H17 responses in a Stat3-dependent manner. Science 326, 986-991 (2009).
13. + T cells in an interleukin-10-dependent manner. Immunity 34, 554-565 (2011).
14. Park, S.-G. et al. T regulatory cells maintain intestinal homeostasis by suppressing γδ T cells. Immunity 33, 791-803 (2010).
15. Cho, S. et al. The class B scavenger receptor CD36 mediates free radical production and tissue injury in cerebral ischemia. J. Neurosci. 25, 2504-2512 (2005).
16. Kunz, A. et al. Neurovascular protection by ischemic tolerance: role of nitric oxide and reactive oxygen species. J. Neurosci. 27, 7083-7093 (2007).
17. Braniste, V. et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med. 6, 263ra158 (2014).
18. Hu, X., Li, P. & Chen, J. Pro: regulatory T cells are protective in ischemic stroke. Stroke 44, e85-e86 (2013).
19. Round, J.L. & Mazmanian, S.K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313-323 (2009).
20. Nishio, J. & Honda, K. Immunoregulation by the gut microbiota. Cell. Mol. Life Sci. 69, 3635-3650 (2012).
21. Justicia, C. et al. Neutrophil infiltration increases matrix metalloproteinase-9 in the ischemic brain after occlusion-reperfusion of the middle cerebral artery in rats. J. Cereb. Blood Flow Metab. 23, 1430-1440 (2003).
22. Stowe, A.M. et al. Neutrophil elastase and neurovascular injury following focal stroke and reperfusion. Neurobiol. Dis. 35, 82-90 (2009).
23. Engelhardt, B. & Ransohoff, R.M. The ins and outs of T lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol. 26, 485-495 (2005).
24. Morton, A.M. et al. Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut. Proc. Natl. Acad. Sci. USA 111, 6696-6701 (2014).
25. Nowotschin, S. & Hadjantonakis, A.-K. Use of KikGR, a photoconvertible green-to-red fluorescent protein, for cell labeling and lineage analysis in ES cells and mouse embryos. BMC Dev. Biol. 9, 49 (2009).
26. + regulatory T cells via a TGF-β- and retinoic acid-dependent mechanism. J. Exp. Med. 204, 1757-1764 (2007).
27. + dendritic cells: master regulators of tolerance? Trends Immunol. 32, 412-419 (2011).
28. Ochoa-Repáraz, J. et al. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 3, 487-495 (2010).
29. Rescigno, M. et al. Dendritic cells express tight-junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2, 361-367 (2001).
30. Niess, J.H. et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307, 254-258 (2005).
31. Josefowicz, S.Z., Lu, L.-F. & Rudensky, A.Y. Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 30, 531-564 (2012).
32. Louveau, A. et al. Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337-341 (2015).
33. Kleinschnitz, C. & Wiendl, H. Con: regulatory T cells are protective in ischemic stroke. Stroke 44, e87-e88 (2013).
34. Kleinschnitz, C. et al. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood 121, 679-691 (2013).
35. Roth, T.L. et al. Transcranial amelioration of inflammation and cell death after brain injury. Nature 505, 223-228 (2014).
36. Pérez-de-Puig, I. et al. Neutrophil recruitment to the brain in mouse and human ischemic stroke. Acta Neuropathol. 129, 239-257 (2015).
37. Kleinschnitz, C. et al. Early detrimental T cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor to thrombus formation. Blood 115, 3835-3842 (2010).
38. Li, G.-Z. et al. Expression of interleukin-17 in ischemic brain tissue. Scand. J. Immunol. 62, 481-486 (2005).
39. Kostulas, N., Pelidou, S.H., Kivisäkk, P., Kostulas, V. & Link, H. Increased IL-1β, IL-8 and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic stroke study. Stroke 30, 2174-2179 (1999).
40. Erbel, C. et al. Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability. Basic Res. Cardiol. 106, 125-134 (2011).
41. Abraham, C. & Cho, J. Interleukin-23-TH 17 pathways and inflammatory bowel disease. Inflamm. Bowel Dis. 15, 1090-1100 (2009).
42. Keller, J.J. et al. Increased risk of stroke among patients with Crohn's disease: a population-based matched cohort study. Int. J. Colorectal Dis. 30, 645-653 (2015).
43. Singh, S., Kullo, I.J., Pardi, D.S. & Loftus, E.V. Jr. Epidemiology, risk factors and management of cardiovascular diseases in IBD. Nat. Rev. Gastroenterol. Hepatol. 12, 26-35 (2015).
44. Kilkenny, C., Browne, W., Cuthill, I.C., Emerson, M. & Altman, D.G. Animal research: reporting in vivo experiments - the ARRIVE guidelines. J. Cereb. Blood Flow Metab. 31, 991-993 (2011).
45. H17 cells by segmented filamentous bacteria. Cell 139, 485-498 (2009).
46. Snel, J. et al. Comparison of 16S rRNA sequences of segmented filamentous bacteria isolated from mice, rats and chickens, and proposal of 'Candidatus arthromitus'. Int. J. Syst. Bacteriol. 45, 780-782 (1995).
47. Barman, M. et al. Enteric salmonellosis disrupts the microbial ecology of the murine gastrointestinal tract. Infect. Immun. 76, 907-915 (2008).
48. Benson, A.K. et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc. Natl. Acad. Sci. USA 107, 18933-18938 (2010).
49. Ubeda, C. et al. Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice. J. Exp. Med. 209, 1445-1456 (2012).
50. Caricilli, A.M. et al. Gut microbiota is a key modulator of insulin resistance in Tlr2-knockout mice. PLoS Biol. 9, e1001212 (2011).
51. Jackman, K., Kunz, A. & Iadecola, C. Modeling focal cerebral ischemia in vivo. Methods Mol. Biol. 793, 195-209 (2011).
52. Lin, T.N., He, Y.Y., Wu, G., Khan,M. & Hsu, C.Y. Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke 24, 117-121 (1993).
53. Bouët, V. et al. Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse. Exp. Neurol. 203, 555-567 (2007).
54. Yagi, S. & Costanzo, R.M. Grafting the olfactory epithelium to the olfactory bulb. Am. J. Rhinol. Allergy 23, 239-243 (2009).
55. Jackman, K. et al. Progranulin deficiency promotes post-ischemic blood-brain barrier disruption. J. Neurosci. 33, 19579-19589 (2013).
56. Schloss, P.D. et al. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 75, 7537-7541 (2009).
57. Buffie, C.G. et al. Precision microbiome reconstitution restores bile acid-mediated resistance to Clostridium difficile. Nature 517, 205-208 (2015).
58. Sheneman, L., Evans, J. & Foster, J.A. Clearcut: a fast implementation of relaxed neighbor joining. Bioinformatics 22, 2823-2824 (2006).
59. Garcia-Bonilla, L., Racchumi, G., Murphy, M., Anrather, J. & Iadecola, C. Endothelial CD36 contributes to postischemic brain injury by promoting neutrophil activation via CSF3. J. Neurosci. 35, 14783-14793 (2015).
60. Pino, P.A. & Cardona, A.E. Isolation of brain and spinal cord mononuclear cells using Percoll gradients. J. Vis. Exp. 48, 2348 (2011).
61. Roederer, M. Spectral compensation for flow cytometry: visualization artifacts, limitations and caveats. Cytometry 45, 194-205 (2001).
62. Liaw, A. & Wiener, M. Classification and regression by randomForest. R News 2, 18-22 (2002).