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Monocytes Contribute to IFN-β Production via the MyD88-Dependent Pathway and Cytotoxic T-Cell Responses against Mucosal Respiratory Syncytial Virus Infection

  • Tae Hoon Kim (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Chae Won Kim (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Dong Sun Oh (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Hi Eun Jung (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Heung Kyu Lee (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST))
  • Received : 2021.06.07
  • Accepted : 2021.07.30
  • Published : 2021.08.31

Abstract

Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children. However, little is known about the contribution of monocytes to antiviral responses against RSV infection. We identified the IFN-β production of monocytes using IFN-β/YFP reporter mice. The kinetic analysis of IFN-β-producing cells in in vivo RSV-infected lung cells indicated that monocytes are recruited to the inflamed lung during the early phase of infection. These cells produced IFN-β via the myeloid differentiation factor 88-mediated pathway, rather than the TLR7- or mitochondrial antiviral signaling protein-mediated pathway. In addition, monocyte-ablated mice exhibited decreased numbers of IFN-γ-producing and RSV Ag-specific CD8+ T cells. Collectively, these data indicate that monocytes play pivotal roles in cytotoxic T-cell responses and act as type I IFN producers during RSV infection.

Keywords

Acknowledgement

Authors would like to thank Dr. Jun Chang at Ewha Womans University for the discussion and technical help. This study was supported by the National Research Foundation of Korea (NRF-2019R1A2C2087490, NRF-2021M3A9D3026428, and NRF-2021M3A9H3015688) funded by the Ministry of Science and ICT of Korea. The authors also thank Drs. Akiko Iwasaki, Suk-Jo Kang, Myoung Ho Jang, and Mi-Na Kweon for mice and reagents.

References

  1. Karron RA. Preventing respiratory syncytial virus (RSV) disease in children. Science 2021;372:686-687. https://doi.org/10.1126/science.abf9571
  2. Efstathiou C, Abidi SH, Harker J, Stevenson NJ. Revisiting respiratory syncytial virus's interaction with host immunity, towards novel therapeutics. Cell Mol Life Sci 2020;77:5045-5058. https://doi.org/10.1007/s00018-020-03557-0
  3. Hijano DR, Vu LD, Kauvar LM, Tripp RA, Polack FP, Cormier SA. Role of type I interferon (IFN) in the respiratory syncytial virus (RSV) immune response and disease severity. Front Immunol 2019;10:566.
  4. Murira A, Lamarre A. Type-I interferon responses: from friend to foe in the battle against chronic viral infection. Front Immunol 2016;7:609.
  5. Guerrero-Plata A, Baron S, Poast JS, Adegboyega PA, Casola A, Garofalo RP. Activity and regulation of alpha interferon in respiratory syncytial virus and human metapneumovirus experimental infections. J Virol 2005;79:10190-10199. https://doi.org/10.1128/JVI.79.16.10190-10199.2005
  6. Oh DS, Kim TH, Lee HK. Differential role of anti-viral sensing pathway for the production of type I interferon β in dendritic cells and macrophages against respiratory syncytial virus A2 strain infection. Viruses 2019;11:62.
  7. Jewell NA, Vaghefi N, Mertz SE, Akter P, Peebles RS Jr, Bakaletz LO, Durbin RK, Flano E, Durbin JE. Differential type I interferon induction by respiratory syncytial virus and influenza a virus in vivo. J Virol 2007;81:9790-9800. https://doi.org/10.1128/JVI.00530-07
  8. Kim TH, Oh DS, Jung HE, Chang J, Lee HK. Plasmacytoid dendritic cells contribute to the production of IFN-β via TLR7-myd88-dependent pathway and CTL priming during respiratory syncytial virus infection. Viruses 2019;11:730.
  9. Hornung V, Schlender J, Guenthner-Biller M, Rothenfusser S, Endres S, Conzelmann KK, Hartmann G. Replication-dependent potent IFN-α induction in human plasmacytoid dendritic cells by a single-stranded RNA virus. J Immunol 2004;173:5935-5943. https://doi.org/10.4049/jimmunol.173.10.5935
  10. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol 2011;30:16-34.  https://doi.org/10.3109/08830185.2010.529976
  11. de Marcken M, Dhaliwal K, Danielsen AC, Gautron AS, Dominguez-Villar M. TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection. Sci Signal 2019;12:eaaw1347.
  12. Scheu S, Dresing P, Locksley RM. Visualization of IFNbeta production by plasmacytoid versus conventional dendritic cells under specific stimulation conditions in vivo. Proc Natl Acad Sci USA 2008;105:20416-20421. https://doi.org/10.1073/pnas.0808537105
  13. Adachi O, Kawai T, Takeda K, Matsumoto M, Tsutsui H, Sakagami M, Nakanishi K, Akira S. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 1998;9:143-150. https://doi.org/10.1016/S1074-7613(00)80596-8
  14. Seo SU, Kwon HJ, Ko HJ, Byun YH, Seong BL, Uematsu S, Akira S, Kweon MN. Type I interferon signaling regulates Ly6C(hi) monocytes and neutrophils during acute viral pneumonia in mice. PLoS Pathog 2011;7:e1001304.
  15. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 2004;101:5598-5603. https://doi.org/10.1073/pnas.0400937101
  16. Sun Q, Sun L, Liu HH, Chen X, Seth RB, Forman J, Chen ZJ. The specific and essential role of MAVS in antiviral innate immune responses. Immunity 2006;24:633-642. https://doi.org/10.1016/j.immuni.2006.04.004
  17. Oh DS, Oh JE, Jung HE, Lee HK. Transient depletion of CD169+ cells contributes to impaired early protection and effector CD8+ T cell recruitment against mucosal respiratory syncytial virus infection. Front Immunol 2017;8:819.
  18. Kim S, Joo DH, Lee JB, Shim BS, Cheon IS, Jang JE, Song HH, Kim KH, Song MK, Chang J. Dual role of respiratory syncytial virus glycoprotein fragment as a mucosal immunogen and chemotactic adjuvant. PLoS One 2012;7:e32226.
  19. Ichinohe T, Lee HK, Ogura Y, Flavell R, Iwasaki A. Inflammasome recognition of influenza virus is essential for adaptive immune responses. J Exp Med 2009;206:79-87. https://doi.org/10.1084/jem.20081667
  20. Sunderkotter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, Leenen PJ. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol 2004;172:4410-4417. https://doi.org/10.4049/jimmunol.172.7.4410
  21. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004;303:1526-1529. https://doi.org/10.1126/science.1093620
  22. Bhoj VG, Sun Q, Bhoj EJ, Somers C, Chen X, Torres JP, Mejias A, Gomez AM, Jafri H, Ramilo O, et al. MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus. Proc Natl Acad Sci U S A 2008;105:14046-14051. https://doi.org/10.1073/pnas.0804717105
  23. Colonna M, Trinchieri G, Liu YJ. Plasmacytoid dendritic cells in immunity. Nat Immunol 2004;5:1219-1226. https://doi.org/10.1038/ni1141
  24. Bencze D, Fekete T, Pazmandi K. Type I interferon production of plasmacytoid dendritic cells under control. Int J Mol Sci 2021;22:4190.
  25. Refolo G, Vescovo T, Piacentini M, Fimia GM, Ciccosanti F. Mitochondrial interactome: a focus on antiviral signaling pathways. Front Cell Dev Biol 2020;8:8.
  26. Demoor T, Petersen BC, Morris S, Mukherjee S, Ptaschinski C, De Almeida Nagata DE, Kawai T, Ito T, Akira S, Kunkel SL, et al. IPS-1 signaling has a nonredundant role in mediating antiviral responses and the clearance of respiratory syncytial virus. J Immunol 2012;189:5942-5953. https://doi.org/10.4049/jimmunol.1201763
  27. Goritzka M, Makris S, Kausar F, Durant LR, Pereira C, Kumagai Y, Culley FJ, Mack M, Akira S, Johansson C. Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes. J Exp Med 2015;212:699-714. https://doi.org/10.1084/jem.20140825
  28. Hou W, Gibbs JS, Lu X, Brooke CB, Roy D, Modlin RL, Bennink JR, Yewdell JW. Viral infection triggers rapid differentiation of human blood monocytes into dendritic cells. Blood 2012;119:3128-3131. https://doi.org/10.1182/blood-2011-09-379479
  29. Schmidt ME, Varga SM. The CD8 t cell response to respiratory virus infections. Front Immunol 2018;9:678.
  30. Graham BS, Bunton LA, Wright PF, Karzon DT. Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. J Clin Invest 1991;88:1026-1033. https://doi.org/10.1172/JCI115362
  31. McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A. Type I interferons in infectious disease. Nat Rev Immunol 2015;15:87-103. https://doi.org/10.1038/nri3787
  32. Kolumam GA, Thomas S, Thompson LJ, Sprent J, Murali-Krishna K. Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J Exp Med 2005;202:637-650. https://doi.org/10.1084/jem.20050821
  33. Soudja SM, Ruiz AL, Marie JC, Lauvau G. Inflammatory monocytes activate memory CD8(+) T and innate NK lymphocytes independent of cognate antigen during microbial pathogen invasion. Immunity 2012;37:549-562. https://doi.org/10.1016/j.immuni.2012.05.029