The role of dendritic cells in immunity against primary herpes simplex virus infections

Frontiers in Microbiology

Volumn 5, Issue OCT, 2014, Pages

  Bedoui, Sammy ^a   Greyer, Marie ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

CD40; Cytokines; Dendritic cells; T cells; Viral immunity

Indexed keywords

CD8 ANTIGEN; CHEMOKINE RECEPTOR CCR7; INTERFERON; INTERLEUKIN 12; INTERLEUKIN 6; MACROPHAGE INFLAMMATORY PROTEIN 3BETA; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 9; UVOMORULIN;

ANTIGEN PRESENTATION; ANTIGEN RECOGNITION; APOPTOSIS; CELL ACTIVATION; CELL MIGRATION; CELLULAR IMMUNITY; CROSS PRESENTATION; CYTOTOXIC T LYMPHOCYTE; DENDRITIC CELL; GENE EXPRESSION; HERPES SIMPLEX; HUMAN; INFECTION CONTROL; NONHUMAN; REVIEW; T LYMPHOCYTE ACTIVATION;

EID: 84987784628     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2014.00533     Document Type: Review

References (88)

1. Ackerman, A. L., and Cresswell, P. (2004). Cellular mechanisms governing cross-presentation of exogenous antigens. Nat. Immunol. 5, 678-684. doi: 10.1038/ni1082
2. Allan, R. S., Smith, C. M., Belz, G. T., Van Lint, A. L., Wakim, L. M., Heath, W. R., et al. (2003). Epidermal viral immunity induced by CD8alpha+ dendritic cells but not by Langerhans cells. Science 301, 1925-1928. doi: 10.1126/science.1087576
3. Allan, R. S., Waithman, J., Bedoui, S., Jones, C. M., Villadangos, J. A., Zhan, Y., et al. (2006). Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity 25, 153-162. doi: 10.1016/j.immuni.2006.04.017
4. Bachem, A., Guttler, S., Hartung, E., Ebstein, F., Schaefer, M., Tannert, A., et al. (2010). Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J. Exp. Med. 207, 1273-1281. doi: 10.1084/jem.20100348
5. Bachem, A., Hartung, E., Guttler, S., Mora, A., Zhou, X., Hegemann, A., et al. (2012). Expression of XCR1 characterizes the batf3-dependent lineage of dendritic cells capable of antigen cross-Presentation. Front. Immunol. 3:214. doi: 10.3389/fimmu.2012.00214
6. Bedoui, S., and Gebhardt, T. (2011). Interaction between dendritic cells and T cells during peripheral virus infections: a role for antigen presentation beyond lymphoid organs? Curr. Opin. Immunol. 23, 124-130. doi: 10.1016/j.coi.2010.11.001
7. Bedoui, S., Prato, S., Mintern, J., Gebhardt, T., Zhan, Y., Lew, A. M., et al. (2009a). Characterization of an immediate splenic precursor of CD8+ dendritic cells capable of inducing antiviral T cell responses. J. Immunol. 182, 4200-4207. doi: 10.4049/jimmunol.0802286
8. Bedoui, S., Whitney, P. G., Waithman, J., Eidsmo, L., Wakim, L., Caminschi, I., et al. (2009b). Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat. Immunol. 10, 488-495. doi: 10.1038/ni.1724
9. Bevan, M. J. (2004). Helping the CD8+ T-cell response. Nat. Rev. Immunol. 4, 595-602. doi: 10.1038/nri1413
10. Bosnjak, L., Miranda-Saksena, M., Koelle, D. M., Boadle, R. A., Jones, C. A., and Cunningham, A. L. (2005). Herpes simplex virus infection of human dendritic cells induces apoptosis and allows cross-presentation via uninfected dendritic cells. J. Immunol. 174, 2220-2227. doi: 10.4049/jimmunol.174.4.2220
11. Bursch, L. S., Wang, L., Igyarto, B., Kissenpfennig, A., Malissen, B., Kaplan, D. H., et al. (2007). Identification of a novel population of Langerin+ dendritic cells. J. Exp. Med. 204, 3147-3156. doi: 10.1084/jem.20071966
12. Carbone, F. R., Belz, G. T., and Heath, W. R. (2004). Transfer of antigen between migrating and lymph node-resident DCs in peripheral T-cell tolerance and immunity. Trends Immunol. 25, 655-658. doi: 10.1016/j.it.2004.09.013
13. Conrady, C. D., Zheng, M., Fitzgerald, K. A., Liu, C., and Carr, D. J. (2012). Resistance to HSV-1 infection in the epithelium resides with the novel innate sensor, IFI-16. Mucosal Immunol. 5, 173-183. doi: 10.1038/mi.2011.63
14. Crozat, K., Guiton, R., Contreras, V., Feuillet, V., Dutertre, C. A., Ventre, E., et al. (2010a). The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells. J. Exp. Med. 207, 1283-1292. doi: 10.1084/jem.20100223
15. Crozat, K., Guiton, R., Guilliams, M., Henri, S., Baranek, T., Schwartz-Cornil, I., et al. (2010b). Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets. Immunol. Rev. 234, 177-198. doi: 10.1111/j.0105-2896.2009.00868.x
16. Cunningham, A. L., Abendroth, A., Jones, C., Nasr, N., and Turville, S. (2010). Viruses and Langerhans cells. Immunol. Cell Biol. 88, 416-423. doi: 10.1038/icb.2010.42
17. Davey, G. M., Wojtasiak, M., Proietto, A. I., Carbone, F. R., Heath, W. R., and Bedoui, S. (2010). Cutting edge: priming of CD8 T cell immunity to herpes simplex virus type 1 requires cognate TLR3 expression in vivo. J. Immunol. 184, 2243-2246. doi: 10.4049/jimmunol.0903013
18. Dominguez, P. M., and Ardavin, C. (2010). Differentiation and function of mouse monocyte-derived dendritic cells in steady state and inflammation. Immunol. Rev. 234, 90-104. doi: 10.1111/j.0105-2896.2009.00876.x
19. Eidsmo, L., Allan, R., Caminschi, I., Van Rooijen, N., Heath, W. R., and Carbone, F. R. (2009). Differential migration of epidermal and dermal dendritic cells during skin infection. J. Immunol. 182, 3165-3172. doi: 10.4049/jimmunol.0802950
20. Frank, G. M., Buela, K. A., Maker, D. M., Harvey, S. A., and Hendricks, R. L. (2012). Early responding dendritic cells direct the local NK response to control herpes simplex virus 1 infection within the cornea. J. Immunol. 188, 1350-1359. doi: 10.4049/jimmunol.1101968
21. Gebhardt, T., Mueller, S. N., Heath, W. R., and Carbone, F. R. (2013). Peripheral tissue surveillance and residency by memory T cells. Trends Immunol. 34, 27-32. doi: 10.1016/j.it.2012.08.008
22. Gebhardt, T., Whitney, P. G., Zaid, A., Mackay, L. K., Brooks, A. G., Heath, W. R., et al. (2011). Different patterns of peripheral migration by memory CD4+ and CD8+ T cells. Nature 477, 216-219. doi: 10.1038/nature10339
23. Halford, W. P., Veress, L. A., Gebhardt, B. M., and Carr, D. J. (1997). Innate and acquired immunity to herpes simplex virus type 1. Virology 236, 328-337. doi: 10.1006/viro.1997.8738
24. Hare, D., and Mossman, K. L. (2013). Novel paradigms of innate immune sensing of viral infections. Cytokine 63, 219-224. doi: 10.1016/j.cyto.2013.06.001
25. Heath, W. R., and Carbone, F. R. (2009). Dendritic cell subsets in primary and secondary T cell responses at body surfaces. Nat. Immunol. 10, 1237-1244. doi: 10.1038/ni.1822
26. Heath, W. R., and Carbone, F. R. (2013). The skin-resident and migratory immune system in steady state and memory: innate lymphocytes, dendritic cells and T cells. Nat. Immunol. 14, 978-985. doi: 10.1038/ni.2680
27. Iijima, N., Mattei, L. M., and Iwasaki, A. (2011). Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue. Proc. Natl. Acad. Sci. U.S.A. 108, 284-289. doi: 10.1073/pnas.1005201108
28. Ishikawa, H., Ma, Z., and Barber, G. N. (2009). STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461, 788-792. doi: 10.1038/nature08476
29. Jiang, A., Bloom, O., Ono, S., Cui, W., Unternaehrer, J., Jiang, S., et al. (2007). Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity 27, 610-624. doi: 10.1016/j.immuni.2007.08.015
30. Jirmo, A. C., Nagel, C. H., Bohnen, C., Sodeik, B., and Behrens, G. M. (2009). Contribution of direct and cross-presentation to CTL immunity against herpes simplex virus 1. J. Immunol. 182, 283-292. doi: 10.4049/jimmunol.182.1.283
31. Joffre, O. P., Segura, E., Savina, A., and Amigorena, S. (2012). Cross-presentation by dendritic cells. Nat. Rev. Immunol. 12, 557-569. doi: 10.1038/nri3254
32. Johnston, C., Koelle, D. M., and Wald, A. (2011). HSV-2: in pursuit of a vaccine. J. Clin. Invest. 121, 4600-4609. doi: 10.1172/JCI57148
33. Jones, C. A., Fernandez, M., Herc, K., Bosnjak, L., Miranda-Saksena, M., Boadle, R. A., et al. (2003). Herpes simplex virus type 2 induces rapid cell death and functional impairment of murine dendritic cells in vitro. J. Virol. 77, 11139-11149. doi: 10.1128/JVI.77.20.11139-11149.2003
34. Kaplan, D. H. (2010). Langerhans cells: not your average dendritic cell. Trends Immunol. 31, 437. doi: 10.1016/j.it.2010.10.003
35. Koelle, D. M., and Corey, L. (2008). Herpes simplex: insights on pathogenesis and possible vaccines. Annu. Rev. Med. 59, 381-395. doi: 10.1146/annurev.med.59.061606.095540
36. Kurts, C., Robinson, B. W., and Knolle, P. A. (2010). Cross-priming in health and disease. Nat. Rev. Immunol. 10, 403-414. doi: 10.1038/nri2780
37. Lauterbach, H., Bathke, B., Gilles, S., Traidl-Hoffmann, C., Luber, C. A., Fejer, G., et al. (2010). Mouse CD8alpha+ DCs and human BDCA3+ DCs are major producers of IFN-lambda in response to poly IC. J. Exp. Med. 207, 2703-2717. doi: 10.1084/jem.20092720
38. Lee, H. K., Zamora, M., Linehan, M. M., Iijima, N., Gonzalez, D., Haberman, A., et al. (2009). Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection. J. Exp. Med. 206, 359-370. doi: 10.1084/jem.20080601
39. Leib, D. A., Harrison, T. E., Laslo, K. M., Machalek, M. A., Moorman, N. J., and Virgin, H. W. (1999). Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. J. Exp. Med. 189, 663-672. doi: 10.1084/jem.189.4.663
40. Leoni, V., Gianni, T., Salvioli, S., and Campadelli-Fiume, G. (2012). Herpes simplex virus glycoproteins gH/gL and gB bind Toll-like receptor 2, and soluble gH/gL is sufficient to activate NF-kappaB. J. Virol. 86, 6555-6562. doi: 10.1128/JVI.00295-12
41. Lund, J. M., Linehan, M. M., Iijima, N., and Iwasaki, A. (2006). Cutting edge: plasmacytoid dendritic cells provide innate immune protection against mucosal viral infection in situ. J. Immunol. 177, 7510-7514. doi: 10.4049/jimmunol.177.11.7510
42. Lund, J., Sato, A., Akira, S., Medzhitov, R., and Iwasaki, A. (2003). Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J. Exp. Med. 198, 513520. doi: 10.1084/jem.20030162
43. Macleod, B. L., Bedoui, S., Hor, J. L., Mueller, S. N., Russell, T. A., Hollett, N. A., et al. (2014). Distinct APC subtypes srive spatially segregated CD4+ and CD8+ T-cell effector activity during skin infection with HSV-1. PLoS Pathog. 10:e1004303. doi: 10.1371/journal.ppat.1004303
44. Malissen, B., Tamoutounour, S., and Henri, S. (2014). The origins and functions of dendritic cells and macrophages in the skin. Nat. Rev. Immunol. 14, 417-428. doi: 10.1038/nri3683
45. Mazzini, E., Massimiliano, L., Penna, G., and Rescigno, M. (2014). Oral tolerance can be established via gap junction transfer of fed antigens from CX3CR1+ macrophages to CD103+ dendritic cells. Immunity 40, 248-261. doi: 10.1016/j.immuni.2013.12.012
46. Merad, M., Ginhoux, F., and Collin, M. (2008). Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol. 8, 935-947. doi: 10.1038/nri2455
47. Merad, M., Sathe, P., Helft, J., Miller, J., and Mortha, A. (2013). The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu. Rev. Immunol. 31, 563-604. doi: 10.1146/annurev-immunol-020711-074950
48. Nair-Gupta, P., Baccarini, A., Tung, N., Seyffer, F., Florey, O., Huang, Y., et al. (2014). TLR Signals Induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation. Cell 158, 506-521. doi: 10.1016/j.cell.2014.04.054
49. Nair-Gupta, P., and Blander, J. M. (2013). An updated view of the intracellular mechanisms regulating cross-presentation. Front. Immunol. 4:401. doi: 10.3389/fimmu.2013.00401
50. Nguyen, M. L., and Blaho, J. A. (2007). Apoptosis during herpes simplex virus infection. Adv. Virus Res. 69, 67-97. doi: 10.1016/S0065-3527(06)69002-7
51. Noisakran, S., and Carr, D. J. (2001). Type I interferons and herpes simplex virus infection: a naked DNA approach as a therapeutic option? Immunol. Res. 24, 1-11. doi: 10.1385/IR:24:1:01
52. Nopora, K., Bernhard, C. A., Ried, C., Castello, A. A., Murphy, K. M., Marconi, P., et al. (2012). MHC class I cross-presentation by dendritic cells counteracts viral immune evasion. Front. Immunol. 3:348. doi: 10.3389/fimmu.2012.00348
53. Peretti, S., Shaw, A., Blanchard, J., Bohm, R., Morrow, G., Lifson, J. D., et al. (2005). Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses. Blood 106, 1305-1313. doi: 10.1182/blood-2004-12-4899
54. Piguet, V. (2005). Receptor modulation in viral replication: HIV, HSV, HHV-8, and HPV: same goal, different techniques to interfere with MHC-I antigen presentation. Curr. Top. Microbiol. Immunol. 285, 199-217. doi: 10.1007/3-540-26764-6_7
55. Prechtel, A. T., Turza, N. M., Kobelt, D. J., Eisemann, J. I., Coffin, R. S., Mcgrath, Y., et al. (2005). Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration. J. Gen. Virol. 86, 1645-1657. doi: 10.1099/vir.0.80852-0
56. Puttur, F. K., Fernandez, M. A., White, R., Roediger, B., Cunningham, A. L., Weninger, W., et al. (2010). Herpes simplex virus infects skin gamma delta T cells before Langerhans cells and impedes migration of infected Langerhans cells by inducing apoptosis and blocking E-cadherin downregulation. J. Immunol. 185, 477-487. doi: 10.4049/jimmunol.0904106
57. Rajasagi, N. K., Kassim, S. H., Kollias, C. M., Zhao, X., Chervenak, R., and Jennings, S. R. (2009). CD4+ T cells are required for the priming of CD8+ T cells following infection with herpes simplex virus type 1. J. Virol. 83, 5256-5268. doi: 10.1128/JVI.01997-08
58. Reis e Sousa, C. (2006). Dendritic cells in a mature age. Nat. Rev. Immunol. 6, 476-483. doi: 10.1038/nri1845
59. Reizis, B. (2012). Classical dendritic cells as a unique immune cell lineage. J. Exp. Med. 209, 1053-1056. doi: 10.1084/jem.20121038
60. Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., et al. (2001). Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2, 361-367. doi: 10.1038/86373
61. Roizman, B., and Whitley, R. J. (2013). An inquiry into the molecular basis of HSV latency and reactivation. Annu. Rev. Microbiol. 67, 355-374. doi: 10.1146/annurev-micro-092412-155654
62. Salio, M., Cella, M., Suter, M., and Lanzavecchia, A. (1999). Inhibition of dendritic cell maturation by herpes simplex virus. Eur. J. Immunol. 29, 3245-3253. doi: 10.1002/(SICI)1521-4141(199910)29:10<3245::AID-IMMU3245>3.0.CO;2-X
63. Sancho-Shimizu, V., Perez De Diego, R., Jouanguy, E., Zhang, S. Y., and Casanova, J. L. (2011). Inborn errors of anti-viral interferon immunity in humans. Curr. Opin. Virol. 1, 487-496. doi: 10.1016/j.coviro.2011.10.016
64. Sato, A., Linehan, M. M., and Iwasaki, A. (2006). Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 103, 17343-17348. doi: 10.1073/pnas.0605102103
65. Schulz, O., Diebold, S. S., Chen, M., Naslund, T. I., Nolte, M. A., Alexopoulou, L., et al. (2005). Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 433, 887-892. doi: 10.1038/nature03326
66. Segura, E., and Villadangos, J. A. (2011). A modular and combinatorial view of the antigen cross-presentation pathway in dendritic cells. Traffic 12, 1677-1685. doi: 10.1111/j.1600-0854.2011.01254.x
67. Shin, H., and Iwasaki, A. (2013). Generating protective immunity against genital herpes. Trends Immunol. 34, 487-494. doi: 10.1016/j.it.2013.08.001
68. Shortman, K., and Heath, W. R. (2010). The CD8+ dendritic cell subset. Immunol. Rev. 234, 18-31. doi: 10.1111/j.0105-2896.2009.00870.x
69. Singh, R., and Cresswell, P. (2010). Defective cross-presentation of viral antigens in GILT-free mice. Science 328, 1394-1398. doi: 10.1126/science.1189176
70. Smith, C. M., Wilson, N. S., Waithman, J., Villadangos, J. A., Carbone, F. R., Heath, W. R., et al. (2004). Cognate CD4+ T cell licensing of dendritic cells in CD8+ T cell immunity. Nat. Immunol. 5, 1143-1148. doi: 10.1038/ni1129
71. St Leger, A. J., and Hendricks, R. L. (2011). CD8+ T cells patrol HSV-1-infected trigeminal ganglia and prevent viral reactivation. J. Neurovirol. 17, 528-534. doi: 10.1007/s13365-011-0062-1
72. Stefanidou, M., Ramos, I., Mas Casullo, V., Trepanier, J. B., Rosenbaum, S., Fernandez-Sesma, A., et al. (2013). Herpes simplex virus 2 (HSV-2) prevents dendritic cell maturation, induces apoptosis, and triggers release of proinflammatory cytokines: potential links to HSV-HIV synergy. J. Virol. 87, 1443-1453. doi: 10.1128/JVI.01302-12
73. Stock, A., Napolitani, G., and Cerundolo, V. (2013). Intestinal DC in migrational imprinting of immune cells. Immunol. Cell Biol. 91, 240-249. doi: 10.1038/icb.2012.73
74. Stock, A. T., Smith, J. M., and Carbone, F. R. (2014). Type I IFN suppresses Cxcr2 driven neutrophil recruitment into the sensory ganglia during viral infection. J. Exp. Med. 211, 751-759. doi: 10.1084/jem.20132183
75. Sun, L., Wu, J., Du, F., Chen, X., and Chen, Z. J. (2013). Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786-791. doi: 10.1126/science.1232458
76. Swiecki, M., Wang, Y., Gilfillan, S., and Colonna, M. (2013). Plasmacytoid dendritic cells contribute to systemic but not local antiviral responses to HSV infections. PLoS Pathog 9:e1003728. doi: 10.1371/journal.ppat.1003728
77. Theodoridis, A. A., Eich, C., Figdor, C. G., and Steinkasserer, A. (2011). Infection of dendritic cells with herpes simplex virus type 1 induces rapid degradation of CYTIP, thereby modulating adhesion and migration. Blood 118, 107-115. doi: 10.1182/blood-2010-07-294363
78. Thery, C., Ostrowski, M., and Segura, E. (2009). Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 9, 581-593. doi: 10.1038/nri2567
79. Unterholzner, L., Keating, S. E., Baran, M., Horan, K. A., Jensen, S. B., Sharma, S., et al. (2010). IFI16 is an innate immune sensor for intracellular DNA. Nat. Immunol. 11, 997-1004. doi: 10.1038/ni.1932
80. van Lint, A., Ayers, M., Brooks, A. G., Coles, R. M., Heath, W. R., and Carbone, F. R. (2004). Herpes simplex virus-specific CD8+ T cells can clear established lytic infections from skin and nerves and can partially limit the early spread of virus after cutaneous inoculation. J. Immunol. 172, 392-397. doi: 10.4049/jimmunol.172.1.392
81. Villadangos, J. A., and Young, L. (2008). Antigen-presentation properties of plasmacytoid dendritic cells. Immunity 29, 352-361. doi: 10.1016/j.immuni.2008.09.002
82. Weber, F., Wagner, V., Rasmussen, S. B., Hartmann, R., and Paludan, S. R. (2006). Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J. Virol. 80, 5059-5064. doi: 10.1128/JVI.80.10.5059-5064.2006
83. Wong, P., and Pamer, E. G. (2003). Feedback regulation of pathogen-specific T cell priming. Immunity 18, 499-511. doi: 10.1016/S1074-7613(03)00081-5
84. Wu, J., Sun, L., Chen, X., Du, F., Shi, H., Chen, C., et al. (2013). Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339, 826-830. doi: 10.1126/science.1229963
85. Yang, J., Huck, S. P., Mchugh, R. S., Hermans, I. F., and Ronchese, F. (2006). Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo. Proc. Natl. Acad. Sci. U.S.A. 103, 147-152. doi: 10.1073/pnas.0509054103
86. Zhang, Z., Yuan, B., Bao, M., Lu, N., Kim, T., and Liu, Y. J. (2011). The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat. Immunol. 12, 959-965. doi: 10.1038/ni.2091
87. Zhao, X., Deak, E., Soderberg, K., Linehan, M., Spezzano, D., Zhu, J., et al. (2003). Vaginal submucosal dendritic cells, but not Langerhans cells, induce protective Th1 responses to herpes simplex virus-2. J. Exp. Med. 197, 153-162. doi: 10.1084/jem.20021109
88. Zhu, J., Peng, T., Johnston, C., Phasouk, K., Kask, A. S., Klock, A., et al. (2013). Immune surveillance by CD8alphaalpha+ skin-resident T cells in human herpes virus infection. Nature 497, 494-497. doi: 10.1038/nature12110