Immune impairment of alveolar macrophage phagocytosis during influenza virus pneumonia
Abstract
The pathogenesis of viral pneumonia is associated with an intact antiviral immune response. To determine the degree of involvement of the host response in influenza virus-induced impairment of pulmonary antibacterial defenses, mice were immunosuppressed by treatment with antilymphocyte serum (ALS). Eight days after infection, pulmonary defense mechanisms were quantitated by aerogenic challenge with Staphylococcus aureus; the ingestion of opsonized erythrocyte (EA) was used to monitor the phagocytic capability of alveolar macrophages obtained by pulmonary lavage. The ALS treatment alone caused no significant alteration in pulmonary antibacterial defenses or macrophage phagocytosis, nor did it interfere with viral multiplication. In noninfected lungs, less than 1% of the initial viable staphylococci remained viable at 24 h compared with proliferation to 490 +/- 147% in virus-infected lungs. Treatment with ALS prevented staphylococcal multiplication, the bactericidal value being 28 +/- 12% at the same time period. The phagocytic index (EA ingested/100 macrophages) in cells retrieved from normal lungs was 783 +/- 22 compared with 235 +/- 29 in macrophages from virus-infected lungs. The ALS ameliorated the impairment in phagocytic ingestion, the index being 505 +/- 34. Incubation of alveolar macrophages from virus-infected, ALS-treated animals with specific viral antibody reestablished the phagocytic defect in a dose-dependent manner; the index being 215 +/- 30 at the lowest dilution of antiviral globulin. The data demonstrate that the virus-induced suppression of pulmonary antibacterial defenses caused by dysfunction in alveolar macrophage phagocytosis is, in part, immunologically mediated.
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Prior viral infections dysregulate both alveolar macrophages and neutrophils, thereby inhibiting bactericidal activity.
“Prior viral infections dysregulate both alveolar macrophages (64, 131–136) and neutrophils (65, 128, 129), thereby inhibiting bactericidal activity.”
From Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia. (2018) · cites this paper as [134]
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Sun, K., & Metzger, D. W. (2008) · Nature Medicine · doi:10.1038/nm1765 · Cited by 587 · see citing works
Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia.
Hanada, S., Pirzadeh, M., Carver, K. Y., & Deng, J. C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02640 · Cited by 495 · see citing works
“Prior viral infections dysregulate both alveolar macrophages (64, (131) (132) (133) (134) (135) (136) and neutrophils (65, 128, 129) , thereby inhibiting bactericidal activity.”
BackgroundType I IFNs mediate development of postinfluenza bacterial pneumonia in mice
Shahangian, A., Chow, E. K., Tian, X., Kang, J. R., Ghaffari, A., Liu, S. Y., Belperio, J. A., Cheng, G., & Deng, J. C. (2009) · Journal of Clinical Investigation · doi:10.1172/jci35412 · Cited by 479 · see citing works
Tate, M. D., Pickett, D. L., van Rooijen, N., Brööks, A. G., & Reading, P. C. (2010) · Journal of Virology · doi:10.1128/jvi.00291-10 · Cited by 226 · see citing works
“Airway M have been implicated in susceptibility to secondary bacterial infections following influenza virus infections (28, 34, 58).”
BackgroundKinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae
Smith, A. M., Adler, F. R., Ribeiro, R. M., Gutenkunst, R. N., McAuley, J., McCullers, J. A., & Perelson, A. S. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003238 · Cited by 195 · see citing works
“Indeed, increased production of IFN{c during the recovery from influenza reduces the ability of alveolar macrophages to phagocytose incoming bacteria [25,29,30], which then contributes to a dysfunctional neutrophil response [23].”
Holt, P. G. (1986) · PubMed · Cited by 188 · see citing works
The role of viral infections in exacerbations of chronic obstructive pulmonary disease and asthma
Hewitt, R., Farne, H. A., Ritchie, A. I., Luke, E., Johnston, S. L., & Mallia, P. (2015) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465815618113 · Cited by 185 · see citing works
“In animal models of postinfluenza bacterial pneumonia, there are impairments in macrophage [Jakab, 1982] and neutrophil responses [McNamee and Harmsen, 2006], and IFN-γ signalling [Sun and Metzger, 2008].”
BackgroundInnate Immune Response of Human Alveolar Macrophages during Influenza A Infection
Wang, J., Nikrad, M. P., Travanty, E. A., Zhou, B., Phang, T., Gao, B., Alford, T., Ito, Y., Nahreini, P., Hartshorn, K. L., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029879 · Cited by 153 · see citing works
“Although impairment of macrophage phagocytosis of bacteria after influenza in mice is well recognized [60,61] and secondary bacterial infection after influenza is a common clinical problem, we were not able to detect a significant decrease in uptake of heat-inactivated S.”
BackgroundInfluenza virus replication in macrophages: balancing protection and pathogenesis
Cline, T. D., Beck, D., & Bianchini, E. A. (2017) · Journal of General Virology · doi:10.1099/jgv.0.000922 · Cited by 113 · see citing works
“pneumoniae co-infection, and the phagocytic capacity of AM from IAV-infected mice is decreased relative to macrophages from uninfected mice [13, 73].”
BackgroundWinther, B., Brofeldt, S., And, B. C., & Mygind, N. (1984) · Acta Oto-Laryngologica · doi:10.3109/00016488409130994 · Cited by 93 · see citing works
Sun, K., Ye, J., Perez, D. R., & Metzger, D. W. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002664 · Cited by 91 · see citing works
Viral-Bacterial Synergistic Interaction in Respiratory Disease
Babiuk, L. A., Lawman, M. J., & Bielefeldt‐Ohmann, H. (1988) · Advances in virus research · doi:10.1016/s0065-3527(08)60713-7 · Cited by 80 · see citing works
The role of respiratory viruses in the etiology of bacterial pneumonia
Lee, K. H., Gordon, A., & Foxman, B. (2016) · Evolution Medicine and Public Health · doi:10.1093/emph/eow007 · Cited by 69 · see citing works
Prasso, J. E., & Deng, J. C. (2016) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2016.11.006 · Cited by 65 · see citing works
Binding of bacteria to HEp-2 cells infected with influenza A virus
Ahmer, O. R. E., Raza, M. W., OGILVIE, M. M., et al. (1999) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.1999.tb01255.x · Cited by 66 · see citing works
Influenza virus-induced immune complexes suppress alveolar macrophage phagocytosis
Astry, C. L., & Jakab, G. J. (1984) · Journal of Virology · doi:10.1128/jvi.50.2.287-292.1984 · Cited by 58 · see citing works
“Indeed, recently we have demonstrated that the transient defect in alveolar macrophage phagocytosis is, in part, mediated by the humoral (10) and cell-mediated (13) antiviral immune response of the host.”
BackgroundSelf-citationIrwin, C., Yoon, K. J., Wang, C., Hoff, S. J., Zimmerman, J. J., Denagamage, T., & O'Connor, A. M. C. (2010) · Applied and Environmental Microbiology · doi:10.1128/aem.02733-09 · Cited by 54 · see citing works
“No study with experiments reporting on virus persistence in wastewater, soil, compost, or under UV light passed quality assessment (17, 34, 46, 71, 94, 101).”
BackgroundViral Infection of Human Lung Macrophages Increases PDL1 Expression via IFNβ
Staples, K. J., Nicholas, B., McKendry, R., Spalluto, C. M., Wallington, J. C., Bragg, C. W., Robinson, E. C., Martin, K., Djukanović, R., & Wilkinson, T. M. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121527 · Cited by 50 · see citing works
“Early studies demonstrated that virus-induced suppression of antibacterial defences was mediated by lymphocytes[21].”
BackgroundLiu, L., Lehmkuhl, H. D., & Kaeberle, M. L. (1999) · PubMed · Cited by 50 · see citing works
Reduction of influenza virus pathogenesis by exposure to 0.5 ppm ozone
Jakab, G. J., & Hmieleski, R. R. (1988) · Journal of Toxicology and Environmental Health · doi:10.1080/15287398809531128 · Cited by 45 · see citing works
Self-citationRaza, M. W., OGILVIE, M. M., Blackwell, C. C., Stewart, J., Elton, R. A., & Weir, D. M. (1993) · Epidemiology and Infection · doi:10.1017/s095026880006828x · Cited by 42 · see citing works
Worgall, S., Singh, R. N., Leopold, P. L., Kaner, R. J., Hackett, N. R., Topf, N., Moore, M. A. S., & Crystal, R. G. (1999) · Blood · doi:10.1182/blood.v93.2.655 · Cited by 42 · see citing works
Oleksiewicz, M. B., & Nielsen, J. P. (1999) · Veterinary Microbiology · doi:10.1016/s0378-1135(98)00309-5 · Cited by 40 · see citing works
Application of Interferons in the Control of Infectious Diseases of Cattle
Babiuk, L. A., Sordillo, L. M., Campos, M., Hughes, H. P. A., Rossi-Campos, A., & Harland, R. (1991) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(91)78635-9 · Cited by 39 · see citing works
Viral–bacterial interactions–therapeutic implications
Deng, J. C. (2013) · Influenza and Other Respiratory Viruses · doi:10.1111/irv.12174 · Cited by 37 · see citing works
“65 Viruses also have multiple effects on immune cells, including innate leukocytes critical to antibacterial host [66] [67] [68] [69] [70] [71] [72] [73] Similarly, RSV and influenza have been shown to depress neutrophil migration, phagocytosis, and bactericidal activity.”
BackgroundBabiuk, L. A., Lawman, M. J., & Gifford, G. (1987) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.31.5.752 · Cited by 37 · see citing works
Rodriguez, A. E., Bogart, C., Gilbert, C. M., McCullers, J. A., Smith, A. M., Kanneganti, T., & Lupfer, C. R. (2019) · PLoS ONE · doi:10.1371/journal.pone.0212236 · Cited by 32 · see citing works
Virus-Induced Enhancement of Arachidonate Metabolism by Bovine Alveolar Macrophages In Vitro
Laegreid, W. W., Taylor, S. M., Leid, R. W., et al. (1989) · Journal of Leukocyte Biology · doi:10.1002/jlb.45.4.283 · Cited by 33 · see citing works
Chung, D. R., & Huh, K. (2015) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.2015.999668 · Cited by 31 · see citing works
“Impairment of the phagocytic function of alveolar macrophages is at least partially mediated by lymphocytes because treatment with antilymphocyte serum has been shown to reverse the impairment in phagocytosis [52].”
BackgroundViral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36
Cooper, G. E., Pounce, Z. C., Wallington, J. C., Bastidas-Legarda, L. Y., Nicholas, B., Chidomere, C. I., Robinson, E. C., Martin, K., Tocheva, A. S., Christodoulides, M., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0163889 · Cited by 27 · see citing works
Defense Mechanisms in the Bovine Lung
Liggitt, H. D. (1985) · Veterinary Clinics of North America Food Animal Practice · doi:10.1016/s0749-0720(15)31330-x · Cited by 25 · see citing works
Hernández, E., Ramisse, F., Gros, P., & Cavallo, J.-D. (2000) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2000.tb01520.x · Cited by 21 · see citing works
Davies, D. H., Long, D. L., McCarthy, A. R., et al. (1986) · Veterinary Microbiology · doi:10.1016/0378-1135(86)90013-1 · Cited by 20 · see citing works
Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense
Pöpperl, P., Stoff, M., & Beineke, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26010407 · Cited by 19 · see citing works
Kodihalli, S., Sivanandan, V., Nagaraja, K. V., Shaw, D., & Halvorson, D. A. (1994) · Avian Diseases · doi:10.2307/1591842 · Cited by 17 · see citing works
The problem of bacterial complications post respiratory viral infections
Egorov, A. (2018) · Microbiology Independent Research Journal (MIR Journal) · doi:10.18527/2500-2236-2018-5-1-12-21 · Cited by 16 · see citing works
“Нарушение антибактериальной активности нейтрофилов и макрофагов за счет уменьшения их количества и фагоцитарной активности в очаге вирусной инфекции [65-67].”
Klonoski, J. M., Watson, T., Bickett, T. E., Svendsen, J. M., Gau, T. J., Britt, A., Nelson, J. T., Schlenker, E. H., Chaussee, M. S., Rynda‐Apple, A., et al. (2018) · Viral Immunology · doi:10.1089/vim.2017.0193 · Cited by 15 · see citing works
“Specifically, a loss of macrophage cell function has been observed historically within superinfection models (5,28,78), with evidence of defects in phagocytosis of bacteria after PR8 infection (70).”
BackgroundSimilarities of host defense mechanisms against pulmonary infectious diseases in animals and man
Green, G. M. (1984) · Journal of Toxicology and Environmental Health · doi:10.1080/15287398409530510 · Cited by 15 · see citing works
Evidence of Immunosuppression by Bovine Respiratory Syncytial Virus
Woldehiwet, Z., & Sharma, R. (1992) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.1992.tb01624.x · Cited by 14 · see citing works
Zaki, S. R., & Paddock, C. D. (2008) · Springer eBooks · doi:10.1007/978-0-387-68792-6_11 · Cited by 14 · see citing works
Influenza enhances host susceptibility to non-pulmonary invasive Streptococcus pyogenes infections
Herrera, A. L., Potts, R. A., Huber, V. C., & Chaussee, M. S. (2023) · Virulence · doi:10.1080/21505594.2023.2265063 · Cited by 13 · see citing works
Pneumonia in US hospitalized patients with influenza-like illness: BioSense, 2007–2010
Benoit, S. R., Burkom, H. S., McIntyre, A. F., Kniss, K. L., Brammer, L., Finelli, L., & Jain, S. (2012) · Epidemiology and Infection · doi:10.1017/s0950268812001549 · Cited by 9 · see citing works
Biochemical strategies of E3 ubiquitin ligases target viruses in critical diseases
Dubey, A. R., Jagtap, Y. A., Kumar, P., Patwa, S. M., Kinger, S., Kumar, A., Singh, S., Prasad, A., Jana, N. R., & Mishra, A. (2021) · Journal of Cellular Biochemistry · doi:10.1002/jcb.30143 · Cited by 8 · see citing works
“The entry of the influenza virus in the lung epithelial cells embarks the innate immunity‐based cellular responses.(121) The identification of the viral particles by different pattern recognition receptors (PRRs) primarily results in formation and release of immunomodulatory molecules.”
BackgroundRoberts, S., Williams, C. M., Salmon, S. L., Bonin, J. L., Metzger, D. W., & Furuya, Y. (2019) · Vaccines · doi:10.3390/vaccines7040146 · Cited by 10 · see citing works
Worgall, S., Singh, R. N., Leopold, P. L., et al. (1999) · Blood · doi:10.1182/blood.v93.2.655.402k02_655_666 · Cited by 8 · see citing works
Burgher, Y., Provost, C., Pesant, M.-J., et al. (2023) · Viruses · doi:10.3390/v15051207 · Cited by 6 · see citing works
“Productive replication of SwIV in macrophages can alter antiviral macrophage functions such as phagocytosis, resulting in enhanced disease severity and impaired bacterial clearance during secondary bacterial infection [47,57].”
BackgroundViral-Bacterial Synergistic Interactions/Pathogenesis in Cattle
Babiuk, L. A., Morsy, M., Campos, M., et al. (1995) · Springer eBooks · doi:10.1007/978-1-4899-0978-7_4 · Cited by 6 · see citing works
Riser, B. L., & Maassab, H. F. (1990) · The Journal of Infectious Diseases · doi:10.1093/infdis/161.4.699 · Cited by 5 · see citing works
“The mortality often associated with influenza is primarily the result of secondary bacterial pneumonia or occasionally viral pneumonia [4-6], and there is evidence to suggest that this complication may be the result of impaired macrophage function [7-11] induced by viral infection.”
BackgroundПроблема бактериальных осложнений при респираторных вирусных инфекциях
Egorov, A. (2018) · Microbiology Independent Research Journal (MIR Journal) · doi:10.18527/2500-2236-2018-5-1-1-11 · Cited by 3 · see citing works
Lung lipid deposition in pneumonias of different etiologiesPreprint
Potashnikova, D. M., Tvorogova, A. V., Komissarov, A. A., Saidova, A. A., Sotnikova, T. N., Makarova, V. O., Arifulin, E. A., Lipina, T., Shirokova, O. M., Melnikov, E. S., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.30.522299 · Cited by 3 · see citing works
“In addition. lipid accumulation may result from tissue decomposition in the inflamed areas, the emergence and the extracellular spread of lipid droplets combined with the macrophages’ inability to eliminate the accumulated lipids [35,36].”
Alcohol and HIV: Experimental and Clinical Evidence of Combined Impact on the Lung
Cribbs, S. K., & Rimland, D. (2013) · Respiratory medicine · doi:10.1007/978-1-4614-8833-0_15 · Cited by 1 · see citing works
YANG, J., Hukkanen, V., Seljelid, R., et al. (1997) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.1997.d01-406.x · Cited by 1 · see citing works
The use of systematic reviews for decision making in animal production medicine and policy
Irwin, C. (2010) · doi:10.31274/etd-180810-396
“For example, systematic reviews of interventions have found an association to be present between treatment effect and whether a study was randomized or blinded, identifying the observation of a stronger effect when treatment groups were not randomized or blinded (10,27,54,55).”
BackgroundFinelli, L., Fiore, A. E., Dhara, R., Brammer, L., Shay, D. K., Kamimoto, L., Fry, A. M., Hageman, J. C., Gorwitz, R. J., Bresee, J., et al. (2008) · PEDIATRICS
A Novel Mechanism of Enhanced Susceptibility to Bacterial Pneumonia in Influenza-infected Hosts
Ghoneim, H. E. (2013) · doi:10.21007/etd.cghs.2013.0108
“Several studies of animal models reported phagocytic dysfunction in AMs during influenza infections [145-148].”
BackgroundPulmonary antibacterial defenses during mild and severe influenza virus infection
Nickerson, C. L., & Jakab, G. J. (1990) · Infection and Immunity · doi:10.1128/iai.58.9.2809-2814.1990 · Cited by 75 · see citing works
“In the case of lower respiratory tract infection, such as that induced by the P12 virus, specific immune mechanisms play a role in mediating phagocytic dysfunction (5, 6, 10).”
BackgroundMethodSelf-citation
- Authors
- Jakab
- Venue
- PubMed
- Publisher
- National Institutes of Health
- Published
- 1982-11-01
- Volume
- 126
- Issue
- 5
- Pages
- 778-82
- OpenAlex
- W1864856913
- Cited by
- 56
- References
- 0
- Citations by year
- 2025: 1 · 2023: 3 · 2021: 1 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 3 · 2013: 4 · 2012: 2
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PubMed (publishedVersion)
- PubMed
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- influenza virus pneumonia, alveolar macrophages, phagocytosis, immunosuppression, antilymphocyte serum, Staphylococcus aureus, host immune response, bacterial clearance
- MeSH terms
- Animals, Antibodies, Viral, Antilymphocyte Serum, Female, Immunosuppression Therapy, Macrophages, Opsonin Proteins, Orthomyxoviridae, Orthomyxoviridae Infections, Phagocytosis, Pneumonia, Viral, Pulmonary Alveoli, Rabbits, Staphylococcus aureus, Mice
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