The Role of Neutrophils During Mild and Severe Influenza Virus Infections of Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Mar 23

PMID 21423798

Citations 124

Authors

Michelle D Tate

Lisa J Ioannidis

Ben Croker

Lorena E Brown

Andrew G Brooks

Patrick C Reading

Affiliations

Soon will be listed here.

Abstract

Neutrophils have been implicated in both protective and pathological responses following influenza virus infections. We have used mAb 1A8 (anti-Ly6G) to specifically deplete LyG6(high) neutrophils and induce neutropenia in mice infected with virus strains known to differ in virulence. Mice were also treated with mAb RB6-8C5 (anti-Ly6C/G or anti-Gr-1), a mAb widely used to investigate the role of neutrophils in mice that has been shown to bind and deplete additional leukocyte subsets. Using mAb 1A8, we confirm the beneficial role of neutrophils in mice infected with virus strains of intermediate (HKx31; H3N2) or high (PR8; H1N1) virulence whereas treatment of mice infected with an avirulent strain (BJx109; H3N2) did not affect disease or virus replication. Treatment of BJx109-infected mice with mAb RB6-8C5 was, however, associated with significant weight loss and enhanced virus replication indicating that other Gr-1(+) cells, not neutrophils, limit disease severity during mild influenza infections.

Citing Articles

Deficient neutrophil responses early in influenza infection promote viral replication and pulmonary inflammation.

Gong H, Worley M, Carver K, Godin C, Deng J PLoS Pathog. 2025; 21(1):e1012449.

PMID: 39823516 PMC: 11845034. DOI: 10.1371/journal.ppat.1012449.

TLR7 Promotes Acute Inflammatory-Driven Lung Dysfunction in Influenza-Infected Mice but Prevents Late Airway Hyperresponsiveness.

Miles M, Liong S, Liong F, Trollope G, Wang H, Brooks R Int J Mol Sci. 2025; 25(24.

PMID: 39769461 PMC: 11678220. DOI: 10.3390/ijms252413699.

IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections.

Creusat F, Jouan Y, Gonzalez L, Barsac E, Ilango G, Lemoine R Sci Adv. 2024; 10(41):eadn3257.

PMID: 39392875 PMC: 11468905. DOI: 10.1126/sciadv.adn3257.

Adenosine Triphosphate Release From Influenza-Infected Lungs Enhances Neutrophil Activation and Promotes Disease Progression.

Ledderose C, Valsami E, Elevado M, Junger W J Infect Dis. 2024; 230(1):120-130.

PMID: 39052721 PMC: 11272046. DOI: 10.1093/infdis/jiad442.

Gasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation.

Speaks S, McFadden M, Zani A, Solstad A, Leumi S, Roettger J Nat Commun. 2024; 15(1):2751.

PMID: 38553499 PMC: 10980740. DOI: 10.1038/s41467-024-47067-0.

References

Sweet C, Smith H . Pathogenicity of influenza virus. Microbiol Rev. 1980; 44(2):303-30. PMC: 373180. DOI: 10.1128/mr.44.2.303-330.1980. View

Perrone L, Plowden J, Garcia-Sastre A, Katz J, Tumpey T . H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice. PLoS Pathog. 2008; 4(8):e1000115. PMC: 2483250. DOI: 10.1371/journal.ppat.1000115. View

Lomas-Neira J, Chung C, Perl M, Gregory S, Biffl W, Ayala A . Role of alveolar macrophage and migrating neutrophils in hemorrhage-induced priming for ALI subsequent to septic challenge. Am J Physiol Lung Cell Mol Physiol. 2005; 290(1):L51-8. DOI: 10.1152/ajplung.00028.2005. View

Tate M, Deng Y, Jones J, Anderson G, Brooks A, Reading P . Neutrophils ameliorate lung injury and the development of severe disease during influenza infection. J Immunol. 2009; 183(11):7441-50. DOI: 10.4049/jimmunol.0902497. View

Reading P, Miller J, Anders E . Involvement of the mannose receptor in infection of macrophages by influenza virus. J Virol. 2000; 74(11):5190-7. PMC: 110872. DOI: 10.1128/jvi.74.11.5190-5197.2000. View

Tumpey T, Chen S, Oakes J, Lausch R . Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea. J Virol. 1996; 70(2):898-904. PMC: 189893. DOI: 10.1128/JVI.70.2.898-904.1996. View

Aldridge A . Role of the neutrophil in septic shock and the adult respiratory distress syndrome. Eur J Surg. 2002; 168(4):204-14. DOI: 10.1080/11024150260102807. View

Matsuzaki J, Tsuji T, Chamoto K, Takeshima T, Sendo F, Nishimura T . Successful elimination of memory-type CD8+ T cell subsets by the administration of anti-Gr-1 monoclonal antibody in vivo. Cell Immunol. 2003; 224(2):98-105. DOI: 10.1016/j.cellimm.2003.08.009. View

Conlan J, NORTH R . Neutrophils are essential for early anti-Listeria defense in the liver, but not in the spleen or peritoneal cavity, as revealed by a granulocyte-depleting monoclonal antibody. J Exp Med. 1994; 179(1):259-68. PMC: 2191333. DOI: 10.1084/jem.179.1.259. View

10.

Fujisawa H . Neutrophils play an essential role in cooperation with antibody in both protection against and recovery from pulmonary infection with influenza virus in mice. J Virol. 2008; 82(6):2772-83. PMC: 2258992. DOI: 10.1128/JVI.01210-07. View

11.

Louria D, BLUMENFELD H, Ellis J, KILBOURNE E, ROGERS D . Studies on influenza in the pandemic of 1957-1958. II. Pulmonary complications of influenza. J Clin Invest. 1959; 38(1 Part 2):213-65. PMC: 444127. DOI: 10.1172/JCI103791. View

12.

Jan de Heer H, Hammad H, Soullie T, Hijdra D, Vos N, Willart M . Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med. 2004; 200(1):89-98. PMC: 2213319. DOI: 10.1084/jem.20040035. View

13.

Cassidy L, Lyles D, Abramson J . Synthesis of viral proteins in polymorphonuclear leukocytes infected with influenza A virus. J Clin Microbiol. 1988; 26(7):1267-70. PMC: 266590. DOI: 10.1128/jcm.26.7.1267-1270.1988. View

14.

Daley J, Thomay A, Connolly M, Reichner J, Albina J . Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J Leukoc Biol. 2007; 83(1):64-70. DOI: 10.1189/jlb.0407247. View

15.

Reading P, Morey L, Crouch E, Anders E . Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. J Virol. 1997; 71(11):8204-12. PMC: 192277. DOI: 10.1128/JVI.71.11.8204-8212.1997. View

16.

Czuprynski C, Brown J, Maroushek N, Wagner R, Steinberg H . Administration of anti-granulocyte mAb RB6-8C5 impairs the resistance of mice to Listeria monocytogenes infection. J Immunol. 1994; 152(4):1836-46. View

17.

Hartshorn K, White M, Shepherd V, Reid K, Jensenius J, Crouch E . Mechanisms of anti-influenza activity of surfactant proteins A and D: comparison with serum collectins. Am J Physiol. 1998; 273(6):L1156-66. DOI: 10.1152/ajplung.1997.273.6.L1156. View

18.

Frankova V . Inhalatory infection of mice with influenza A0/PR8 virus. I. The site of primary virus replication and its spread in the respiratory tract. Acta Virol. 1975; 19(1):29-34. View

19.

Zhao Y, Lu M, Lau L, Lu J, Gao Z, Liu J . Neutrophils may be a vehicle for viral replication and dissemination in human H5N1 avian influenza. Clin Infect Dis. 2008; 47(12):1575-8. PMC: 7107848. DOI: 10.1086/593196. View

20.

Egan C, Sukhumavasi W, Bierly A, Denkers E . Understanding the multiple functions of Gr-1(+) cell subpopulations during microbial infection. Immunol Res. 2008; 40(1):35-48. DOI: 10.1007/s12026-007-0061-8. View