J Pediatr Infect Dis
DOI: 10.1055/s-0044-1779444
Review Article

Innate Immune Response-Mediated Inflammation in Viral Pneumonia

Weiwei Ni
1   Department of Neonatology, Taizhou Second People's Hospital, Taizhou, Jiangsu Province, China
,
Xin Wei
2   Department of Chronic Diseases, Disease Prevention and Vaccination Center of Chengyang District, Qingdao, Shandong, China
,
Rui Wu
3   Department of Endocrinology, Geriatric Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei Province, China
› Author Affiliations
Funding None.

Abstract

Objective This study aims to investigate the intricate interactions between viral infections, specifically within the context of community-acquired pneumonia. We seek to shed light on the underestimation of viral pneumonia cases, utilizing advancements in molecular diagnostic testing.

Methods The investigation involves a comprehensive review of existing literature to explore the prevalence and impact of various viruses causing pneumonia in both children and adults. Our focus spans parainfluenza virus, respiratory syncytial virus, human bocavirus, human metapneumovirus, and rhinoviruses in children and coronaviruses, rhinoviruses, and influenza viruses in adults. The study further delves into the host's innate immune response, emphasizing the roles of pattern recognition receptors (PRRs), type I interferons (IFNs), proinflammatory cytokines, and other immune cells during viral infections.

Results The analysis reveals a substantial global burden of viral community-acquired pneumonia, estimating approximately 200 million cases annually in children and adults combined. This study underscores viruses' significant, previously underestimated role in causing pneumonia. Insights into specific viruses affecting different age groups and their prevalence in various geographical settings are provided.

Conclusion In conclusion, this review emphasizes the necessity of recognizing the substantial contribution of viral infections to community-acquired pneumonia cases. The host's innate immune response, mediated by PRRs, type I IFNs, and other immune mediators, is pivotal in preventing viral invasion and replication. The study accentuates the importance of continued research into understanding the innate immune mechanisms involved in viral infections and the resulting inflammation.



Publication History

Received: 09 August 2023

Accepted: 27 December 2023

Article published online:
11 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Kaysin A, Viera AJ. Community-acquired pneumonia in adults: diagnosis and management. Am Fam Physician 2016; 94 (09) 698-706
  • 2 Cilloniz C, Martin-Loeches I, Garcia-Vidal C, San Jose A, Torres A. Microbial etiology of pneumonia: epidemiology, diagnosis and resistance patterns. Int J Mol Sci 2016; 17 (12) 2120
  • 3 Ticona JH, Zaccone VM, McFarlane IM. Community-acquired pneumonia: a focused review. Am J Med Case Rep 2021; 9 (01) 45-52
  • 4 Troeger C, Blacker B, Khalil IA. et al; GBD 2016 Lower Respiratory Infections Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis 2018; 18 (11) 1191-1210
  • 5 Huijts SM, Coenjaerts FEJ, Bolkenbaas M, van Werkhoven CH, Grobbee DE, Bonten MJM. CAPiTA study team. The impact of 13-valent pneumococcal conjugate vaccination on virus-associated community-acquired pneumonia in elderly: exploratory analysis of the CAPiTA trial. Clin Microbiol Infect 2018; 24 (07) 764-770
  • 6 Freeman AM, Leigh Jr TR. Viral Pneumonia. Treasure Island, FL: Stat Pearls; 2018
  • 7 Jain S. Epidemiology of viral pneumonia. Clin Chest Med 2017; 38 (01) 1-9
  • 8 Darden DB, Hawkins RB, Larson SD, Iovine NM, Prough DS, Efron PA. The clinical presentation and immunology of viral pneumonia and implications for management of coronavirus disease 2019. Crit Care Explor 2020; 2 (04) e0109
  • 9 Grief SN, Loza JK. Guidelines for the evaluation and treatment of pneumonia. Prim Care 2018; 45 (03) 485-503
  • 10 Dandachi D, Rodriguez-Barradas MC. Viral pneumonia: etiologies and treatment. J Investig Med 2018; 66 (06) 957-965
  • 11 Pawelek KA, Huynh GT, Quinlivan M, Cullinane A, Rong L, Perelson AS. Modeling within-host dynamics of influenza virus infection including immune responses. PLOS Comput Biol 2012; 8 (06) e1002588
  • 12 Braciale TJ, Sun J, Kim TS. Regulating the adaptive immune response to respiratory virus infection. Nat Rev Immunol 2012; 12 (04) 295-305
  • 13 Vivier E, Malissen B. Innate and adaptive immunity: specificities and signaling hierarchies revisited. Nat Immunol 2005; 6 (01) 17-21
  • 14 Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol 2010; 125 (2, Suppl 2): S33-S40
  • 15 Dropulic LK, Cohen JI. Severe viral infections and primary immunodeficiencies. Clin Infect Dis 2011; 53 (09) 897-909
  • 16 Jiang C, Chen Q, Xie M. Smoking increases the risk of infectious diseases: a narrative review. Tob Induc Dis 2020; 18: 60
  • 17 Raju S, Siddharthan T, McCormack MC. Indoor air pollution and respiratory health. Clin Chest Med 2020; 41 (04) 825-843
  • 18 Munteanu C, Schwartz B. The relationship between nutrition and the immune system. Front Nutr 2022; 9: 1082500
  • 19 Horimoto T, Kawaoka Y. Influenza: lessons from past pandemics, warnings from current incidents. Nat Rev Microbiol 2005; 3 (08) 591-600
  • 20 Garten R, Blanton L, Elal AIA. et al. Update: influenza activity in the United States during the 2017–18 season and composition of the 2018–19 influenza vaccine. MMWR Morb Mortal Wkly Rep 2018; 67 (22) 634-642
  • 21 Kamali A, Holodniy M. Influenza treatment and prophylaxis with neuraminidase inhibitors: a review. Infect Drug Resist 2013; 6: 187-198
  • 22 Rossman JS, Lamb RA. Influenza virus assembly and budding. Virology 2011; 411 (02) 229-236
  • 23 Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J 2015; 45 (05) 1463-1478
  • 24 Rust MJ, Lakadamyali M, Zhang F, Zhuang X. Assembly of endocytic machinery around individual influenza viruses during viral entry. Nat Struct Mol Biol 2004; 11 (06) 567-573
  • 25 Pinto LH, Lamb RA. The M2 proton channels of influenza A and B viruses. J Biol Chem 2006; 281 (14) 8997-9000
  • 26 Denney L, Ho LP. The role of respiratory epithelium in host defence against influenza virus infection. Biomed J 2018; 41 (04) 218-233
  • 27 Fujikura D, Miyazaki T. Programmed cell death in the pathogenesis of influenza. Int J Mol Sci 2018; 19 (07) 2065
  • 28 White SR. Apoptosis and the airway epithelium. J Allergy (Cairo) 2011; 2011: 948406
  • 29 Gregory DJ, Kobzik L. Influenza lung injury: mechanisms and therapeutic opportunities. Am J Physiol Lung Cell Mol Physiol 2015; 309 (10) L1041-L1046
  • 30 Vareille M, Kieninger E, Edwards MR, Regamey N. The airway epithelium: soldier in the fight against respiratory viruses. Clin Microbiol Rev 2011; 24 (01) 210-229
  • 31 Chung EY, Kim SJ, Ma XJ. Regulation of cytokine production during phagocytosis of apoptotic cells. Cell Res 2006; 16 (02) 154-161
  • 32 Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 1995; 146 (01) 3-15
  • 33 Thapa RJ, Ingram JP, Ragan KB. et al. DAI senses influenza A virus genomic RNA and activates RIPK3-dependent cell death. Cell Host Microbe 2016; 20 (05) 674-681
  • 34 Zhirnov OP, Ksenofontov AL, Kuzmina SG, Klenk HD. Interaction of influenza A virus M1 matrix protein with caspases. Biochemistry (Mosc) 2002; 67 (05) 534-539
  • 35 Klomp M, Ghosh S, Mohammed S, Nadeem Khan M. From virus to inflammation, how influenza promotes lung damage. J Leukoc Biol 2021; 110 (01) 115-122
  • 36 McCullers JA, Bartmess KC. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J Infect Dis 2003; 187 (06) 1000-1009
  • 37 Alymova IV, Samarasinghe A, Vogel P, Green AM, Weinlich R, McCullers JA. A novel cytotoxic sequence contributes to influenza A viral protein PB1-F2 pathogenicity and predisposition to secondary bacterial infection. J Virol 2014; 88 (01) 503-515
  • 38 Smith AM, Adler FR, Ribeiro RM. et al. Kinetics of coinfection with influenza A virus and Streptococcus pneumoniae. PLoS Pathog 2013; 9 (03) e1003238
  • 39 McAuley JL, Hornung F, Boyd KL. et al. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe 2007; 2 (04) 240-249
  • 40 Smith AM, McCullers JA. Secondary bacterial infections in influenza virus infection pathogenesis. Curr Top Microbiol Immunol 2014; 385: 327-356
  • 41 Malik G, Zhou Y. Innate immune sensing of influenza A virus. Viruses 2020; 12 (07) 755
  • 42 Lion T. Adenovirus infections in immunocompetent and immunocompromised patients. Clin Microbiol Rev 2014; 27 (03) 441-462
  • 43 Gupta P, Tobias JD, Goyal S. et al. Prolonged mechanical support in children with severe adenoviral infections: a case series and review of the literature. J Intensive Care Med 2011; 26 (04) 267-272
  • 44 Chen X, Lv J, Qin L, Zou C, Tang L. Severe adenovirus pneumonia requiring extracorporeal membrane oxygenation support in immunocompetent children. Front Pediatr 2020; 8: 162
  • 45 Ou Z-Y, Zeng Q-Y, Wang F-H. et al. Retrospective study of adenovirus in autopsied pulmonary tissue of pediatric fatal pneumonia in South China. BMC Infect Dis 2008; 8 (01) 122
  • 46 Ison M, Hayden R. Adenovirus. Microbiol Spectr 2016;4(04)
  • 47 Hemmat N, Baghi HB. The interaction of human papillomaviruses and adeno-associated viruses in suppressive co-infections. Infect Genet Evol 2019; 73: 66-70
  • 48 Castro-Rodriguez JA, Daszenies C, Garcia M, Meyer R, Gonzales R. Adenovirus pneumonia in infants and factors for developing bronchiolitis obliterans: a 5-year follow-up. Pediatr Pulmonol 2006; 41 (10) 947-953
  • 49 Wenman WM, Pagtakhan RD, Reed MH, Chernick V, Albritton W. Adenovirus bronchiolitis in Manitoba: epidemiologic, clinical, and radiologic features. Chest 1982; 81 (05) 605-609
  • 50 Zheng R, Li Y, Chen D. et al. Changes of host immunity mediated by IFN-γ+ CD8+ T cells in children with adenovirus pneumonia in different severity of illness. Viruses 2021; 13 (12) 2384
  • 51 Fan H, Lu B, Cao C. et al. Plasma TNFSF13B and TNFSF14 function as inflammatory indicators of severe adenovirus pneumonia in pediatric patients. Front Immunol 2021; 11: 614781
  • 52 Wang H, Li Z-Y, Liu Y. et al. Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14. Nat Med 2011; 17 (01) 96-104
  • 53 Zhang J, Ma K, Wang X. et al. Desmoglein 2 (DSG2) is a receptor of human adenovirus type 55 causing adult severe community-acquired pneumonia. Virol Sin 2021; 36 (06) 1400-1410
  • 54 Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald KA. Pattern recognition receptors and the innate immune response to viral infection. Viruses 2011; 3 (06) 920-940
  • 55 Perlman S, Netland J. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 2009; 7 (06) 439-450
  • 56 Wu F, Zhao S, Yu B. et al. A new coronavirus associated with human respiratory disease in China. Nature 2020; 579 (7798) 265-269
  • 57 Mathewson AC, Bishop A, Yao Y. et al. Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2. J Gen Virol 2008; 89 (Pt 11): 2741-2745
  • 58 Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 2020; 94 (07) 127
  • 59 Perlman S. Another decade, another coronavirus. N Engl J Med 2020; 20; 382 (08) 760-762
  • 60 Rodriguez-Morales AJ, Bonilla-Aldana DK, Balbin-Ramon GJ. et al. History is repeating itself: probable zoonotic spillover as the cause of the 2019 novel coronavirus epidemic. Infez Med 2020; 28 (01) 3-5
  • 61 Mann R, Perisetti A, Gajendran M, Gandhi Z, Umapathy C, Goyal H. Clinical characteristics, diagnosis, and treatment of major coronavirus outbreaks. Front Med (Lausanne) 2020; 7: 581521
  • 62 Du W, Yu J, Wang H. et al. Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China. Infection 2020; 48 (03) 445-452
  • 63 Fumagalli A, Misuraca C, Bianchi A. et al. Long-term changes in pulmonary function among patients surviving to COVID-19 pneumonia. Infection 2022; 50 (04) 1019-1022
  • 64 Cao W, Li T. COVID-19: towards understanding of pathogenesis. Cell Res 2020; 30 (05) 367-369
  • 65 Sarkesh A, Daei Sorkhabi A, Sheykhsaran E. et al. Extrapulmonary clinical manifestations in COVID-19 patients. Am J Trop Med Hyg 2020; 103 (05) 1783-1796
  • 66 Yamada T, Takaoka A. Innate immune recognition against SARS-CoV-2. Inflamm Regen 2023; 43 (01) 7
  • 67 Heinonen S, Rodriguez-Fernandez R, Diaz A, Oliva Rodriguez-Pastor S, Ramilo O, Mejias A. Infant immune response to respiratory viral infections. Immunol Allergy Clin North Am 2019; 39 (03) 361-376
  • 68 Lozano R, Naghavi M, Foreman K. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380 (9859) 2095-2128
  • 69 Smith EC, Popa A, Chang A, Masante C, Dutch RE. Viral entry mechanisms: the increasing diversity of paramyxovirus entry. FEBS J 2009; 276 (24) 7217-7227
  • 70 Esposito S, Bianchini S, Argentiero A, Neglia C, Principi N. How does one choose the appropriate pharmacotherapy for children with lower respiratory tract infections?. Expert Opin Pharmacother 2020; 21 (14) 1739-1747
  • 71 Rey-Jurado E, Kalergis AM. Immunological features of respiratory syncytial virus-caused pneumonia—implications for vaccine design. Int J Mol Sci 2017; 18 (03) 556
  • 72 Bosis S, Esposito S, Niesters HG. et al. Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences. Clin Microbiol Infect 2008; 14 (07) 677-684
  • 73 Bianchini S, Silvestri E, Argentiero A, Fainardi V, Pisi G, Esposito S. Role of respiratory syncytial virus in pediatric pneumonia. Microorganisms 2020; 8 (12) 2048
  • 74 Lay MK, González PA, León MA. et al. Advances in understanding respiratory syncytial virus infection in airway epithelial cells and consequential effects on the immune response. Microbes Infect 2013; 15 (03) 230-242
  • 75 Roe M, O'Donnell DR, Tasker RC. Respiratory viruses in the intensive care unit. Paediatr Respir Rev 2003; 4 (03) 166-171
  • 76 Henrickson KJ. Parainfluenza viruses. Clin Microbiol Rev 2003; 16 (02) 242-264
  • 77 Moscona A. Entry of parainfluenza virus into cells as a target for interrupting childhood respiratory disease. J Clin Invest 2005; 115 (07) 1688-1698
  • 78 Castleman WL, Northrop PJ, McAllister PK. Replication of parainfluenza type-3 virus and bovine respiratory syncytial virus in isolated bovine type-II alveolar epithelial cells. Am J Vet Res 1991; 52 (06) 880-885
  • 79 Castleman WL, Brundage-Anguish LJ, Kreitzer L, Neuenschwander SB. Pathogenesis of bronchiolitis and pneumonia induced in neonatal and weanling rats by parainfluenza (Sendai) virus. Am J Pathol 1987; 129 (02) 277-286
  • 80 Welliver RC, Wong DT, Middleton Jr E, Sun M, McCarthy N, Ogra PL. Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection. J Pediatr 1982; 101 (06) 889-896
  • 81 Porter DD, Prince GA, Hemming VG, Porter HG. Pathogenesis of human parainfluenza virus 3 infection in two species of cotton rats: Sigmodon hispidus develops bronchiolitis, while Sigmodon fulviventer develops interstitial pneumonia. J Virol 1991; 65 (01) 103-111
  • 82 Branche AR, Falsey AR. Parainfluenza virus infection. In: Seminars in Respiratory and Critical Care Medicine. Thieme Medical Publishers; 2016
  • 83 Williams DJ, Shah SS. Community-acquired pneumonia in the conjugate vaccine era. J Pediatric Infect Dis Soc 2012; 1 (04) 314-328
  • 84 Jain S, Finelli L. CDC EPIC Study Team. Community-acquired pneumonia among U.S. children. N Engl J Med 2015; 372 (22) 2167-2168
  • 85 Parks GD, Alexander-Miller MA. Paramyxovirus activation and inhibition of innate immune responses. J Mol Biol 2013; 425 (24) 4872-4892
  • 86 Falsey AR, Branche AR. Rhinoviruses. Int Encyclopedia Publ Health 2017; 363
  • 87 Nascimento-Carvalho AC, Vilas-Boas AL, Fontoura MH, Vuorinen T, Nascimento-Carvalho CM. PNEUMOPAC-Efficacy Study Group. Respiratory viruses among children with non-severe community-acquired pneumonia: a prospective cohort study. J Clin Virol 2018; 105: 77-83
  • 88 Toivonen L, Schuez-Havupalo L, Karppinen S. et al. Rhinovirus infections in the first 2 years of life. Pediatrics 2016; 138 (03) e20161309
  • 89 Tsolia MN, Psarras S, Bossios A. et al. Etiology of community-acquired pneumonia in hospitalized school-age children: evidence for high prevalence of viral infections. Clin Infect Dis 2004; 39 (05) 681-686
  • 90 Jacobs SE, Lamson DM, St George K, Walsh TJ. Human rhinoviruses. Clin Microbiol Rev 2013; 26 (01) 135-162
  • 91 Gern JE. The ABCs of rhinoviruses, wheezing, and asthma. J Virol 2010; 84 (15) 7418-7426
  • 92 Malmström K, Pitkäranta A, Carpen O. et al. Human rhinovirus in bronchial epithelium of infants with recurrent respiratory symptoms. J Allergy Clin Immunol 2006; 118 (03) 591-596
  • 93 Jakiela B, Brockman-Schneider R, Amineva S, Lee W-M, Gern JE. Basal cells of differentiated bronchial epithelium are more susceptible to rhinovirus infection. Am J Respir Cell Mol Biol 2008; 38 (05) 517-523
  • 94 Miller EK, Bugna J, Libster R. et al. Human rhinoviruses in severe respiratory disease in very low birth weight infants. Pediatrics 2012; 129 (01) e60-e67
  • 95 Bartlett NW, Walton RP, Edwards MR. et al. Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Nat Med 2008; 14 (02) 199-204
  • 96 Bochkov YA, Gern JE. Rhinoviruses and their receptors: implications for allergic disease. Curr Allergy Asthma Rep 2016; 16 (04) 30
  • 97 Bochkov YA, Watters K, Ashraf S. et al. Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication. Proc Natl Acad Sci U S A 2015; 112 (17) 5485-5490
  • 98 Bønnelykke K, Sleiman P, Nielsen K. et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet 2014; 46 (01) 51-55
  • 99 Ganjian H, Rajput C, Elzoheiry M, Sajjan U. Rhinovirus and innate immune function of airway epithelium. Front Cell Infect Microbiol 2020; 10: 277
  • 100 Mizgerd JP. Molecular mechanisms of neutrophil recruitment elicited by bacteria in the lungs. In: Seminars in immunology. Elsevier; 2002
  • 101 Brinkmann V, Reichard U, Goosmann C. et al. Neutrophil extracellular traps kill bacteria. Science 2004; 303 (5663) 1532-1535
  • 102 Bordon J, Aliberti S, Fernandez-Botran R. et al. Understanding the roles of cytokines and neutrophil activity and neutrophil apoptosis in the protective versus deleterious inflammatory response in pneumonia. Int J Infect Dis 2013; 17 (02) e76-e83
  • 103 Pechous RD. With friends like these: the complex role of neutrophils in the progression of severe pneumonia. Front Cell Infect Microbiol 2017; 7: 160
  • 104 Narasaraju T, Yang E, Samy RP. et al. Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol 2011; 179 (01) 199-210
  • 105 Pauksens K, Fjaertoft G, Douhan-Håkansson L, Venge P. Neutrophil and monocyte receptor expression in uncomplicated and complicated influenza A infection with pneumonia. Scand J Infect Dis 2008; 40 (04) 326-337
  • 106 Liu J, Liu Y, Xiang P. et al. Neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage. J Transl Med 2020; 18 (01) 206
  • 107 Holliday ZM, Alnijoumi MM, Reed MA. et al. Neutrophils and secondary infections in COVID-19 induced acute respiratory distress syndrome. New Microbes New Infect 2021; 44: 100944
  • 108 Rudd JM, Pulavendran S, Ashar HK. et al. Neutrophils induce a novel chemokine receptors repertoire during influenza pneumonia. Front Cell Infect Microbiol 2019; 9: 108
  • 109 Högner K, Wolff T, Pleschka S. et al. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS Pathog 2013; 9 (02) e1003188
  • 110 Hou XQ, Gao YW, Yang ST, Wang CY, Ma ZY, Xia XZ. Role of macrophage migration inhibitory factor in influenza H5N1 virus pneumonia. Acta Virol 2009; 53 (04) 225-231
  • 111 Han S, Xu J, Guo X, Huang M. Curcumin ameliorates severe influenza pneumonia via attenuating lung injury and regulating macrophage cytokines production. Clin Exp Pharmacol Physiol 2018; 45 (01) 84-93
  • 112 Cardani A, Boulton A, Kim TS, Braciale TJ. Alveolar macrophages prevent lethal influenza pneumonia by inhibiting infection of type-1 alveolar epithelial cells. PLoS Pathog 2017; 13 (01) e1006140
  • 113 Sakuma R, Morita N, Tanaka Y, Koide N, Komatsu T. Sendai virus C protein affects macrophage function, which plays a critical role in modulating disease severity during Sendai virus infection in mice. Microbiol Immunol 2022; 66 (03) 124-134
  • 114 Channappanavar R, Selvaraj M, More S, Perlman S. Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and severe disease. Vet Pathol 2022; 59 (04) 627-638
  • 115 Zucchini N, Crozat K, Baranek T, Robbins SH, Altfeld M, Dalod M. Natural killer cells in immunodefense against infective agents. Expert Rev Anti Infect Ther 2008; 6 (06) 867-885
  • 116 Cook KD, Waggoner SN, Whitmire JK. NK cells and their ability to modulate T cells during virus infections. Crit Rev Immunol 2014; 34 (05) 359-388
  • 117 Frank K, Paust S. Dynamic natural killer cell and T cell responses to influenza infection. Front Cell Infect Microbiol 2020; 10: 425
  • 118 Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol 2016; 16 (07) 407-420
  • 119 Sharma D, Kanneganti T-D. The cell biology of inflammasomes: mechanisms of inflammasome activation and regulation. J Cell Biol 2016; 213 (06) 617-629
  • 120 Zeng J, Xie X, Feng X-L. et al. Specific inhibition of the NLRP3 inflammasome suppresses immune overactivation and alleviates COVID-19 like pathology in mice. EBioMedicine 2022; 75: 103803
  • 121 Jia X, Liu B, Bao L. et al. Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration. PLoS Pathog 2018; 14 (11) e1007428
  • 122 Chen Y-J, Wang S-F, Weng I-C. et al. Galectin-3 enhances avian H5N1 influenza a virus–induced pulmonary inflammation by promoting NLRP3 inflammasome activation. Am J Pathol 2018; 188 (04) 1031-1042
  • 123 Kawai T, Akira S. Pathogen recognition with Toll-like receptors. Curr Opin Immunol 2005; 17 (04) 338-344
  • 124 Kawai T, Akira S. Innate immune recognition of viral infection. Nat Immunol 2006; 7 (02) 131-137
  • 125 Pasare C, Medzhitov R. Toll-like receptors: linking innate and adaptive immunity. Microbes Infect 2004; 6 (15) 1382-1387
  • 126 Poux C, Dondalska A, Bergenstråhle J. et al. A single-stranded oligonucleotide inhibits toll-like receptor 3 activation and reduces influenza A (H1N1) infection. Front Immunol 2019; 10: 2161
  • 127 Tuvim MJ, Gilbert BE, Dickey BF, Evans SE. Synergistic TLR2/6 and TLR9 activation protects mice against lethal influenza pneumonia. PLoS One 2012; 7 (01) e30596
  • 128 Goffic L. Detrimental contribution of the Toll-like receptor (TLR) 3 to influenza A virus-induced acute pneumonia. PLoS Pathog 2007; 3: e187
  • 129 Zhang L, Zhang B, Wang L, Lou M, Shen Y. Huanglian-Houpo drug combination ameliorates H1N1-induced mouse pneumonia via cytokines, antioxidant factors and TLR/MyD88/NF-κB signaling pathways. Exp Ther Med 2021; 21 (05) 1-11
  • 130 Tanaka A, Nakamura S, Seki M. et al. Toll-like receptor 4 agonistic antibody promotes innate immunity against severe pneumonia induced by coinfection with influenza virus and Streptococcus pneumoniae. Clin Vaccine Immunol 2013; 20 (07) 977-985
  • 131 Alzahrani B, Gaballa MMS, Tantawy AA, Moussa MA, Shoulah SA, Elshafae SM. Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury. J Pathol Transl Med 2022; 56 (02) 81-91
  • 132 Iwata-Yoshikawa N, Nagata N, Takaki H. et al. Prophylactic vaccine targeting TLR3 on dendritic cells ameliorates eosinophilic pneumonia in a mouse SARS-CoV infection model. Immunohorizons 2022; 6 (04) 275-282
  • 133 Monticelli LA, Sonnenberg GF, Abt MC. et al. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol 2011; 12 (11) 1045-1054
  • 134 Spits H, Bernink JH, Lanier L. NK cells and type 1 innate lymphoid cells: partners in host defense. Nat Immunol 2016; 17 (07) 758-764
  • 135 Spits H, Mjösberg J. Heterogeneity of type 2 innate lymphoid cells. Nat Rev Immunol 2022; 22 (11) 701-712
  • 136 Shannon JP, Vrba SM, Reynoso GV. et al. Group 1 innate lymphoid-cell-derived interferon-γ maintains anti-viral vigilance in the mucosal epithelium. Immunity 2021; 54 (02) 276-290.e5
  • 137 Krabbendam L, Bal SM, Spits H, Golebski K. New insights into the function, development, and plasticity of type 2 innate lymphoid cells. Immunol Rev 2018; 286 (01) 74-85
  • 138 Silver JS, Kearley J, Copenhaver AM. et al. Inflammatory triggers associated with exacerbations of COPD orchestrate plasticity of group 2 innate lymphoid cells in the lungs. Nat Immunol 2016; 17 (06) 626-635
  • 139 Li T, Wang J, Wang Y. et al. Respiratory influenza virus infection induces memory-like liver NK cells in mice. J Immunol 2017; 198 (03) 1242-1252
  • 140 Wang Z, Zheng T, Zhu Z. et al. Interferon γ induction of pulmonary emphysema in the adult murine lung. J Exp Med 2000; 192 (11) 1587-1600
  • 141 Freeman CM, Han MK, Martinez FJ. et al. Cytotoxic potential of lung CD8(+) T cells increases with chronic obstructive pulmonary disease severity and with in vitro stimulation by IL-18 or IL-15. J Immunol 2010; 184 (11) 6504-6513
  • 142 Tait Wojno ED, Beamer CA. Isolation and identification of innate lymphoid cells (ILCs) for immunotoxicity testing. Methods Mol Biol 2018; :1803: 353-370
  • 143 Fonseca W, Lukacs NW, Elesela S, Malinczak C-A. Role of ILC2 in viral-induced lung pathogenesis. Front Immunol 2021; 12: 675169
  • 144 Starkey MR, McKenzie AN, Belz GT, Hansbro PM. Pulmonary group 2 innate lymphoid cells: surprises and challenges. Mucosal Immunol 2019; 12 (02) 299-311
  • 145 Sastre B, García-García ML, Cañas JA. et al. Bronchiolitis and recurrent wheezing are distinguished by type 2 innate lymphoid cells and immune response. Pediatr Allergy Immunol 2021; 32 (01) 51-59
  • 146 Lechner AJ, Driver IH, Lee J. et al. Recruited monocytes and type 2 immunity promote lung regeneration following pneumonectomy. Cell Stem Cell 2017; 21 (01) 120-134.e7
  • 147 Chang Y-J, Kim HY, Albacker LA. et al. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat Immunol 2011; 12 (07) 631-638
  • 148 Hoffmann JP, Kolls JK, McCombs JE. Regulation and function of ILC3s in pulmonary infections. Front Immunol 2021; 12: 672523
  • 149 Stehle C, Hernández DC, Romagnani C. Innate lymphoid cells in lung infection and immunity. Immunol Rev 2018; 286 (01) 102-119
  • 150 Das S, St Croix C, Good M. et al. Interleukin-22 inhibits respiratory syncytial virus production by blocking virus-mediated subversion of cellular autophagy. iScience 2020; 23 (07) 101256
  • 151 Kumar P, Thakar MS, Ouyang W, Malarkannan S. IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection. Mucosal Immunol 2013; 6 (01) 69-82
  • 152 Boast A, Curtis N, Holschier J. et al; RCH COVID-19 Treatment Working Group. An approach to the treatment of children with COVID-19. Pediatr Infect Dis J 2022; 41 (08) 654-662
  • 153 Liu JM, Chi J. Is COVID-19-associated cytokine storm distinct from non-COVID-19 secondary hemophagocytic lymphohistiocytosis?. Exp Biol Med (Maywood) 2022; 247 (04) 330-337
  • 154 Rendon A, Rendon-Ramirez EJ, Rosas-Taraco AG. Relevant cytokines in the management of community-acquired pneumonia. Curr Infect Dis Rep 2016; 18 (03) 10
  • 155 Rodriguez-Ramirez HG, Salinas-Carmona MC, Barboza-Quintana O. et al. CD206+ cell number differentiates influenza A (H1N1)pdm09 from seasonal influenza A virus in fatal cases. Mediators Inflamm 2014; 2014: 921054
  • 156 Bystrom J, Al-Adhoubi N, Al-Bogami M, Jawad AS, Mageed RA. Th17 lymphocytes in respiratory syncytial virus infection. Viruses 2013; 5 (03) 777-791