Gammaherpesvirus Alters Alveolar Macrophages According to the Host Genetic Background and Promotes Beneficial Inflammatory Control over Pneumovirus Infection
[en] Human respiratory syncytial virus (hRSV) infection brings a wide spectrum of clinical outcomes, from a mild cold to severe bronchiolitis or even acute interstitial pneumonia. Among the known factors influencing this clinical diversity, genetic background has often been mentioned. In parallel, recent evidence has also pointed out that an early infectious experience affects heterologous infections severity. Here, we analyzed the importance of these two host-related factors in shaping the immune response in pneumoviral disease. We show that a prior gammaherpesvirus infection improves, in a genetic background-dependent manner, the immune system response against a subsequent lethal dose of pneumovirus primary infection notably by inducing a systematic expansion of the CD8+ bystander cell pool and by modifying the resident alveolar macrophages (AMs) phenotype to induce immediate cyto/chemokinic responses upon pneumovirus exposure, thereby drastically attenuating the host inflammatory response without affecting viral replication. Moreover, we show that these AMs present similar rapid and increased production of neutrophil chemokines both in front of pneumoviral or bacterial challenge, confirming recent studies attributing a critical antibacterial role of primed AMs. These results corroborate other recent studies suggesting that the innate immunity cells are themselves capable of memory, a capacity hitherto reserved for acquired immunity.
Disciplines :
Immunology & infectious disease
Author, co-author :
Gilliaux, Gautier ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Santé et pathologies de la faune sauvage
Desmecht, Daniel ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Language :
English
Title :
Gammaherpesvirus Alters Alveolar Macrophages According to the Host Genetic Background and Promotes Beneficial Inflammatory Control over Pneumovirus Infection
Publication date :
06 January 2022
Journal title :
Viruses
eISSN :
1999-4915
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
Nair, H.; Nokes, D.J.; Gessner, B.D.; Dherani, M.; Madhi, S.A.; Singleton, R.J.; Brien, K.L.O.; Roca, A.; Munywoki, P.K.; Kartasasmita, C.; et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis. Lancet 2010, 375, 1545–1555. [CrossRef]
Sun, Y.; López, C. The innate immune response to RSV: Advances in our understanding of critical viral and host factors. Vaccine 2017, 35, 481–488. [CrossRef]
Andeweg, S.P.; Schepp, R.M.; Van De Kassteele, J.; Mollema, L.; Berbers, G.A.M.; Van Boven, M. Population-based serology reveals risk factors for RSV infection in children younger than 5 years. Sci. Rep. 2021, 11, 8953. [CrossRef] [PubMed]
Shi, T.; Balsells, E.; Singleton, R.; Rasmussen, A.; Zar, H.J.; Rath, A.; Madhi, S.A.; Vaccari, L.C.; Bulkow, L.R.; Thomas, E.D.; et al. Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta–analysis. J. Glob. Health 2015, 5, 020416. [CrossRef] [PubMed]
Choi, E.H.; Lee, H.J.; Yoo, T.; Chanock, S.J. A Common Haplotype of Interleukin-4 Gene IL4 Is Associated with Severe Respiratory Syncytial Virus Disease in Korean Children. J. Infect. Dis. 2002, 186, 1207–1211. [CrossRef]
Hoebee, B.; Rietveld, E.; Bont, L.; Van Oosten, M.; Hodemaekers, H.M.; Nagelkerke, N.J.D.; Neijens, H.J.; Kimpen, J.L.L.; Kimman, T.G. Association of Severe Respiratory Syncytial Virus Bronchiolitis with Interleukin-4 and Interleukin-4 Receptor a Polymorphisms. J. Infect. Dis. 2003, 187, 2–11. [CrossRef]
Puthothu, B.; Krueger, M.; Forster, J.; Heinzmann, A. Association between Severe Respiratory Syncytial Virus Infection and IL13/IL4 Haplotypes. J. Infect. Dis. 2006, 193, 438–441. [CrossRef]
Tapia, L.I.; Ampuero, S.; Palomino, M.A.; Luchsinger, V.; Aguilar, N.; Ayarza, E.; Mamani, R.; Larrañaga, C. Infection, Genetics and Evolution Respiratory syncytial virus infection and recurrent wheezing in Chilean infants: A genetic background? Infect. Genet. Evol. 2013, 16, 54–61. [CrossRef]
Wilson, J.; Rowlands, K.; Rockett, K.; Moore, C.; Lockhart, E.; Sharland, M.; Kwiatkowski, D.; Hull, J. Genetic Variation at the IL10 Gene Locus Is Associated with Severity of Respiratory Syncytial Virus Bronchiolitis. J. Infect. Dis. 2005, 191, 1705–1709. [CrossRef]
Zhang, M.; Lu, Y.; Zhang, X.; Lu, A.; Wang, L.; Chen, C. Interleukin-4 polymorphism is associated with severity of respiratory syncytial virus infection. J. Paediatr. Child Health 2016, 52, 25–29. [CrossRef] [PubMed]
Fonseca, W.; Lukacs, N.W.; Ptaschinski, C. Factors Affecting the immunity to Respiratory Syncytial virus: From epigenetics to Microbiome. Front. Microbiol. 2018, 9, 1–15. [CrossRef]
Brodin, P.; Jojic, V.; Gao, T.; Bhattacharya, S.; Angel, C.J.L.; Furman, D.; Shen-Orr, S.; Dekker, C.L.; Swan, G.E.; Butte, A.J.; et al. Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences. Cell 2015, 160, 37–47. [CrossRef] [PubMed]
Machiels, B.; Dourcy, M.; Xiao, X.; Javaux, J.; Mesnil, C.; Sabatel, C.; Desmecht, D.; Lallemand, F.; Martinive, P.; Hammad, H.; et al. A gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes. Nat. Immunol. 2017, 18, 1310–1320. [CrossRef]
Dowd, J.B.; Palermo, T.; Brite, J.; Mcdade, T.W.; Aiello, A. Seroprevalence of Epstein-Barr Virus Infection in U.S. Children Ages 6–19, 2003–2010. PLoS ONE 2013, 8, e64921. [CrossRef] [PubMed]
Netea, M.; Domínguez-Andrés, J.; Barreiro, L.B.; Chavakis, T.; Divangahi, M.; Fuchs, E.; Joosten, L.; van der Meer, J.; Mhlanga, M.; Mulder, W.; et al. Defining trained immunity and its role in health and disease. Nat. Rev. Immunol. 2020, 20, 375–388. [CrossRef]
Divangahi, M.; Aaby, P.; Khader, S.A.; Barreiro, L.B.; Bekkering, S.; Chavakis, T.; Van Crevel, R.; Curtis, N.; Dinardo, A.R.; Dominguez-Andres, J.; et al. Trained immunity, tolerance, priming and differentiation: Distinct immunological processes. Nat. Immunol. 2021, 22, 2–6. [CrossRef]
Rosenberg, H.F.; Domachowske, J.B. Pneumonia virus of mice: Severe respiratory infection in a natural host. Immunol. Lett. 2008, 118, 6–12. [CrossRef]
Bem, R.A.; Domachowske, J.B.; Rosenberg, H.F. Animal models of human respiratory syncytial virus disease. Am. J. Physiol. Lung Cell. Mol. Physiol. 2011, 4, L148–L156. [CrossRef] [PubMed]
Dyer, K.D.; Garcia-Crespo, K.E.; Glineur, S.; Domachowske, J.B.; Rosenberg, H.F. The pneumonia virus of mice (PVM) model of acute respiratory infection. Viruses 2012, 4, 3494–3510. [CrossRef]
Stewart, D.; Fulton, W.B.; Wilson, C.; Monitto, C.L.; Paidas, C.N.; Reeves, R.H.; De Maio, A. Genetic contribution to the septic response in a mouse model. Shock 2002, 18, 342–347. [CrossRef] [PubMed]
Hsieh, C.; Macatonia, S.E.; Garra, A.O.; Murphy, K.M. T Cell Genetic Background Determines Default T Helper Phenotype Development In Vitro. J. Exp. Med. 1995, 181, 713–721. [CrossRef] [PubMed]
Mills, C.D.; Kincaid, K.; Alt, J.M.; Heilman, M.J.; Hill, A.M. M-1/M-2 Macrophages and the Th1/Th2 Paradigm. J. Immunol. 2000, 164, 6166–6173. [CrossRef]
Anh, D.B.T.; Faisca, P.; Desmecht, D.J.-M. Differential resistance/susceptibility patterns to pneumovirus infection among inbred mouse strains. Am. J. Physiol. Lung Cell. Mol. Physiol. 2006, 291, L426–L435. [CrossRef]
Hashimoto, D.; Chow, A.; Noizat, C.; Teo, P.; Beasley, M.B.; Leboeuf, M.; Becker, C.D.; See, P.; Price, J.; Lucas, D.; et al. Tissue-Resident Macrophages Self-Maintain Locally throughout Adult Life with Minimal Contribution from Circulating Monocytes. Immunity 2013, 38, 792–804. [CrossRef]
Yao, Y.; Jeyanathan, M.; Haddadi, S.; Barra, N.G.; Vaseghi-Shanjani, M.; Damjanovic, D.; Lai, R.; Afkhami, S.; Chen, Y.; Dvorkin-Gheva, A.; et al. Induction of Autonomous Memory Alveolar Macrophages Requires T Cell Help and Is Critical to Trained Immunity. Cell 2018, 175, 1634–1650.e17. [CrossRef]
Roquilly, A.; Jacqueline, C.; Davieau, M.; Mollé, A.; Sadek, A.; Fourgeux, C.; Rooze, P.; Broquet, A.; Misme-Aucouturier, B.; Chaumette, T.; et al. Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparal-ysis. Nat. Immunol. 2020, 21, 636–648. [CrossRef] [PubMed]
Kim, T.S.; Braciale, T.J. Respiratory Dendritic Cell Subsets Differ in Their Capacity to Support the Induction of Virus-Specific Cytotoxic CD8+ T Cell Responses. PLoS ONE 2009, 4, e4204. [CrossRef]
Beauchamp, N.M.; Busick, R.Y.; Alexander-Miller, M.A. Functional Divergence among CD103+ Dendritic Cell Subpopulations following Pulmonary Poxvirus Infection. J. Virol. 2010, 84, 10191–10199. [CrossRef]
Dermine, M.; Desmecht, D. In vivo modulation of the innate response to pneumovirus by type-I and-III interferon-induced Bos taurus Mx1. J. Interferon Cytokine Res. 2012, 32, 332–337. [CrossRef] [PubMed]
Haring, J.S.; Pewe, L.L.; Perlman, S.; Alerts, E. Bystander CD8 T Cell-Mediated Demyelination After Viral Infection of the Central Nervous System. J. Immunol. 2002, 169, 1550–1555. [CrossRef] [PubMed]
Tough, D.F.; Sprent, J. Viruses and T Cell Turnover: Evidence for Bystander Proliferation. Immunol. Rev. 1996, 150, 129–142. [CrossRef]
Chen, A.M.; Khanna, N.; Stohlman, S.A.; Bergmann, C.C. Virus-specific and bystander CD8 T cells recruited during virus-induced encephalomyelitis. J. Virol. 2005, 79, 4700–4708. [CrossRef]
Ehl, S.; Hombach, J.; Aichele, P.; Hengartner, H.; Zinkernagel, R.M. Bystander activation of cytotoxic T cells: Studies on the mechanism and evaluation of in vivo significance in a transgenic mouse model. J. Exp. Med. 1997, 185, 1241–1251. [CrossRef]
Murali-Krishna, K.; Altman, J.D.; Suresh, M.; Sourdive, D.J.D.; Zajac, A.J.; Miller, J.D.; Slansky, J.; Ahmed, R. Counting Antigen-Specific CD8 T Cells: A Reevaluation of Bystander Activation during Viral Infection. Immunity 1998, 8, 177–187. [CrossRef]
Zarozinski, C.C.; Welsh, R.M. Minimal bystander activation of CD8T cells during the virus-induced polyclonal T cell response. J. Exp. Med. 1997, 185, 1629–1639. [CrossRef]
Dourcy, M.; Maquet, C.; Dams, L.; Gilliaux, G.; Javaux, J.; Desmecht, D.; Mack, M.; Dewals, B.G.; Machiels, B.; Gillet, L. A gammaherpesvirus licenses CD8 T cells to protect the host from pneumovirus-induced immunopathologies. Mucosal Immunol. 2020, 13, 799–813. [CrossRef] [PubMed]
Guo, H.; Baker, S.F.; Martinez-Sobrido, L.; Topham, D.J. Induction of CD8 T Cell Heterologous Protection by a Single Dose of Single-Cycle Infectious Influenza Virus. J. Virol. 2014, 88, 12006–12016. [CrossRef] [PubMed]
Guilliams, M.; Lambrecht, B.N.; Hammad, H. Division of labor between lung dendritic cells and macrophages in the defense against pulmonary infections. Mucosal Immunol. 2013, 6, 464–473. [CrossRef]
Misharin, A.V.; Morales-Nebreda, L.; Reyfman, P.A.; Cuda, C.M.; Walter, J.M.; McQuattie-Pimentel, A.C.; Chen, C.-I.; Anekalla, K.R.; Joshi, N.; Williams, K.J.N.; et al. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. J. Exp. Med. 2017, 214, 2387–2404. [CrossRef]
Epelman, S.; Lavine, K.J.; Beaudin, A.E.; Sojka, D.K.; Carrero, J.A.; Calderon, B.; Brija, T.; Gautier, E.L.; Ivanov, S.; Satpathy, A.T.; et al. Embryonic and Adult-Derived Resident Cardiac Macrophages Are Maintained through Distinct Mechanisms at Steady State and during Inflammation. Immunity 2014, 40, 91–104. [CrossRef]
Califano, D.; Furuya, Y.; Metzger, D.W. Effects of Influenza on Alveolar Macrophage Viability Are Dependent on Mouse Genetic Strain. J. Immunol. 2018, 201, 134–144. [CrossRef]
Ghoneim, H.E.; Thomas, P.G.; McCullers, J.A. Depletion of Alveolar Macrophages during Influenza Infection Facilitates Bacterial Superinfections. J. Immunol. 2013, 191, 1250–1259. [CrossRef] [PubMed]
Sun, K.; Metzger, D.W. Inhibition of pulmonary antibacterial defense by interferon-γ during recovery from influenza infection. Nat. Med. 2008, 14, 558–564. [CrossRef] [PubMed]
Janssen, W.J.; Barthel, L.; Muldrow, A.; Oberley-Deegan, R.E.; Kearns, M.T.; Jakubzick, C.; Henson, P.M. Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury. Am. J. Respir. Crit. Care Med. 2011, 184, 547–560. [CrossRef]
Seo, S.U.; Kwon, H.J.; Ko, H.J.; Byun, Y.H.; Seong, B.L.; Uematsu, S.; Akira, S.; Kweon, M.N. Type I interferon signaling regulates Ly6Chi monocytes and neutrophils during acute viral pneumonia in mice. PLoS Pathog. 2011, 7, e1001304. [CrossRef] [PubMed]
Lin, K.L.; Suzuki, Y.; Nakano, H.; Ramsburg, E.; Gunn, M.D. CCR2 + Monocyte-Derived Dendritic Cells and Exudate Macrophages Produce Influenza-Induced Pulmonary Immune Pathology and Mortality. J. Immunol. 2008, 180, 2562–2572. [CrossRef]
Arts, R.J.W.; Moorlag, S.J.C.F.M.; Novakovic, B.; Li, Y.; Wang, S.Y.; Oosting, M.; Kumar, V.; Xavier, R.J.; Wijmenga, C.; Joosten, L.A.B.; et al. BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell Host Microbe 2018, 23, 89–100.e5. [CrossRef] [PubMed]
Walsh, E.E.; Peterson, D.R.; Kalkanoglu, A.E.; Lee, F.E.H.; Falsey, A.R. Viral shedding and immune responses to respiratory syncytial virus infection in older adults. J. Infect. Dis. 2013, 207, 1424–1432. [CrossRef] [PubMed]
Tabarani, C.; Bonville, C.; Suryadevara, M.; Branigan, P.; Wang, D.; Huang, D.; Rosenberg, H.; Domachowske, J. Novel Inflammatory Markers, Clinical Risk Factors, and Virus Type Associated with Severe Respiratory Syncytial Virus Infection. Pediatr. Infect. Dis. J. 2013, 32, e437–e442. [CrossRef] [PubMed]
Paquette, S.G.; Banner, D.; Zhao, Z.; Fang, Y.; Huang, S.S.H.; León, A.J.; Ng, D.C.K.; Almansa, R.; Martin-Loeches, I.; Ramirez, P.; et al. Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza A infection. PLoS ONE 2012, 7, e38214. [CrossRef]
To, K.F.; Chan, P.K.S.; Chan, K.F.; Lee, W.K.; Lam, W.Y.; Wong, K.F.; Tang, N.L.S.; Tsang, D.N.C.; Sung, R.Y.T.; Buckley, T.A.; et al. Pathology of fatal human infection associated with avian influenza A H5N1 virus. J. Med. Virol. 2001, 63, 242–246. [CrossRef]
Van Reeth, K. Cytokines in the pathogenesis of influenza. Vet. Microbiol. 2000, 74, 109–116. [CrossRef]
Dienz, O.; Rud, J.G.; Eaton, S.M.; Lanthier, P.A.; Burg, E.; Drew, A.; Bunn, J.; Suratt, B.T.; Haynes, L.; Rincon, M. Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung. Mucosal Immunol. 2012, 5, 258–266. [CrossRef] [PubMed]
Lauder, S.N.; Jones, E.; Smart, K.; Bloom, A.; Williams, A.S.; Hindley, J.P.; Ondondo, B.; Taylor, P.R.; Clement, M.; Fielding, C.; et al. Interleukin-6 limits influenza-induced inflammation and protects against fatal lung pathology. Eur. J. Immunol. 2013, 43, 2613–2625. [CrossRef]
Percopo, C.M.; Ma, M.; Brenner, T.A.; Krumholz, J.O.; Break, T.J.; Laky, K.; Rosenberg, H.F. Critical Adverse Impact of IL-6 in Acute Pneumovirus Infection. J. Immunol. 2019, 202, 871–882. [CrossRef]
Rigaux, P.; Killoran, K.E.; Qiu, Z.; Rosenberg, H.F. Depletion of alveolar macrophages prolongs survival in response to acute pneumovirus infection. Virology 2012, 422, 338–345. [CrossRef]
Pant, K.; Chandrasekaran, A.; Chang, C.J.; Vageesh, A.; Popkov, A.J.; Weinberg, J.B. Effects of tumor necrosis factor on viral replication and pulmonary inflammation during acute mouse adenovirus type 1 respiratory infection. Virology 2020, 547, 12–19. [CrossRef] [PubMed]
Peper, R.L.; Van Campen, H. Tumor necrosis factor as a mediator of inflammation in influenza a viral pneumonia. Microb. Pathog. 1995, 19, 175–183. [CrossRef]
Tuazon Kels, M.; Ng, E.; Al Rumaih, Z.; Pandey, P.; Ruuls, S.; Korner, H.; Newsome, T.; Chaudhri, G.; Karupiah, G. TNF deficiency dysregulates inflammatory cytokine production, leading to lung pathology and death during respiratory poxvirus infection. Proc. Natl. Acad. Sci. USA 2020, 117, 15935–15946. [CrossRef]
Bonville, C.A.; Easton, A.J.; Rosenberg, H.F.; Domachowske, J.B. Altered Pathogenesis of Severe Pneumovirus Infection in Response to Combined Antiviral and Specific Immunomodulatory Agents. J. Virol. 2003, 77, 1237–1244. [CrossRef] [PubMed]
McNamara, P.S.; Ritson, P.; Selby, A.; Hart, C.A.; Smyth, R.L. Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis. Arch. Dis. Child. 2003, 88, 922–926. [CrossRef] [PubMed]
Welliver, T.P.; Garofalo, R.P.; Hosakote, Y.; Hintz, K.H.; Avendano, L.; Sanchez, K.; Velozo, L.; Jafri, H.; Chavez-Bueno, S.; Ogra, P.L.; et al. Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. J. Infect. Dis. 2007, 195, 1126–1136. [CrossRef]
Everard, M.L.; Swarbrick, A.; Wrightham, M.; Mcintyre, J.; Dunkley, C.; James, P.D.; Sewell, H.F.; Milner, A.D. Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection. Arch. Dis. Child. 1994, 71, 428–432. [CrossRef] [PubMed]
Makino, A.; Shibata, T.; Nagayasu, M.; Hosoya, I.; Nishimura, T.; Nakano, C.; Nagata, K.; Ito, T.; Takahashi, Y.; Nakamura, S. RSV infection-elicited high MMP-12–producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration. iScience 2021, 24, 103201. [CrossRef] [PubMed]