The Role of Neutrophils and Neutrophil Elastase in Pneumococcal Pneumonia

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2021 Apr 2

PMID 33796475

Citations 27

Authors

Hisanori Domon

Yutaka Terao

Affiliations

Soon will be listed here.

Abstract

, also known as pneumococcus, is a Gram-positive diplococcus and a major human pathogen. This bacterium is a leading cause of bacterial pneumonia, otitis media, meningitis, and septicemia, and is a major cause of morbidity and mortality worldwide. To date, studies on have mainly focused on the role of its virulence factors including toxins, cell surface proteins, and capsules. However, accumulating evidence indicates that in addition to these studies, knowledge of host factors and host-pathogen interactions is essential for understanding the pathogenesis of pneumococcal diseases. Recent studies have demonstrated that neutrophil accumulation, which is generally considered to play a critical role in host defense during bacterial infections, can significantly contribute to lung injury and immune subversion, leading to pneumococcal invasion of the bloodstream. Here, we review bacterial and host factors, focusing on the role of neutrophils and their elastase, which contribute to the progression of pneumococcal pneumonia.

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References

Boxio R, Wartelle J, Nawrocki-Raby B, Lagrange B, Malleret L, Hirche T . Neutrophil elastase cleaves epithelial cadherin in acutely injured lung epithelium. Respir Res. 2016; 17(1):129. PMC: 5067913. DOI: 10.1186/s12931-016-0449-x. View

Yamada K, Yanagihara K, Araki N, Harada Y, Morinaga Y, Izumikawa K . In vivo efficacy of KRP-109, a novel elastase inhibitor, in a murine model of severe pneumococcal pneumonia. Pulm Pharmacol Ther. 2011; 24(6):660-5. DOI: 10.1016/j.pupt.2011.08.001. View

Berry A, Yother J, Briles D, HANSMAN D, Paton J . Reduced virulence of a defined pneumolysin-negative mutant of Streptococcus pneumoniae. Infect Immun. 1989; 57(7):2037-42. PMC: 313838. DOI: 10.1128/iai.57.7.2037-2042.1989. View

Czaikoski P, Mota J, Nascimento D, Sonego F, Vargas E Silva Castanheira F, Melo P . Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis. PLoS One. 2016; 11(2):e0148142. PMC: 4743982. DOI: 10.1371/journal.pone.0148142. View

Domon H, Maekawa T, Isono T, Furuta K, Kaito C, Terao Y . Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia. Sci Rep. 2021; 11(1):2432. PMC: 7843615. DOI: 10.1038/s41598-021-82212-5. View

Hahn I, Klaus A, Janze A, Steinwede K, Ding N, Bohling J . Cathepsin G and neutrophil elastase play critical and nonredundant roles in lung-protective immunity against Streptococcus pneumoniae in mice. Infect Immun. 2011; 79(12):4893-901. PMC: 3232647. DOI: 10.1128/IAI.05593-11. View

Yanagihara K, Fukuda Y, Seki M, Izumikawa K, Miyazaki Y, Hirakata Y . Effects of specific neutrophil elastase inhibitor, sivelestat sodium hydrate, in murine model of severe pneumococcal pneumonia. Exp Lung Res. 2007; 33(2):71-80. DOI: 10.1080/01902140701198500. View

Narasaraju T, Yang E, Perumal Samy R, Ng H, Poh W, Liew A . Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol. 2011; 179(1):199-210. PMC: 3123873. DOI: 10.1016/j.ajpath.2011.03.013. View

Mizikova I, Ruiz-Camp J, Steenbock H, Madurga A, Vadasz I, Herold S . Collagen and elastin cross-linking is altered during aberrant late lung development associated with hyperoxia. Am J Physiol Lung Cell Mol Physiol. 2015; 308(11):L1145-58. DOI: 10.1152/ajplung.00039.2015. View

10.

Wartha F, Beiter K, Albiger B, Fernebro J, Zychlinsky A, Normark S . Capsule and D-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular traps. Cell Microbiol. 2007; 9(5):1162-71. DOI: 10.1111/j.1462-5822.2006.00857.x. View

11.

Mikacenic C, Moore R, Dmyterko V, West T, Altemeier W, Liles W . Neutrophil extracellular traps (NETs) are increased in the alveolar spaces of patients with ventilator-associated pneumonia. Crit Care. 2018; 22(1):358. PMC: 6307268. DOI: 10.1186/s13054-018-2290-8. View

12.

Aikawa N, Ishizaka A, Hirasawa H, Shimazaki S, Yamamoto Y, Sugimoto H . Reevaluation of the efficacy and safety of the neutrophil elastase inhibitor, Sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study. Pulm Pharmacol Ther. 2011; 24(5):549-54. DOI: 10.1016/j.pupt.2011.03.001. View

13.

Tuomanen E, Liu H, Hengstler B, Zak O, Tomasz A . The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infect Dis. 1985; 151(5):859-68. DOI: 10.1093/infdis/151.5.859. View

14.

Witzenrath M, Gutbier B, Owen J, Schmeck B, Mitchell T, Mayer K . Role of platelet-activating factor in pneumolysin-induced acute lung injury. Crit Care Med. 2007; 35(7):1756-62. DOI: 10.1097/01.CCM.0000269212.84709.23. View

15.

Kovtun A, Messerer D, Scharffetter-Kochanek K, Huber-Lang M, Ignatius A . Neutrophils in Tissue Trauma of the Skin, Bone, and Lung: Two Sides of the Same Coin. J Immunol Res. 2018; 2018:8173983. PMC: 5937416. DOI: 10.1155/2018/8173983. View

16.

Hirst R, Yesilkaya H, Clitheroe E, Rutman A, Dufty N, Mitchell T . Sensitivities of human monocytes and epithelial cells to pneumolysin are different. Infect Immun. 2002; 70(2):1017-22. PMC: 127723. DOI: 10.1128/IAI.70.2.1017-1022.2002. View

17.

Hammerschmidt S, Wolff S, Hocke A, Rosseau S, Muller E, Rohde M . Illustration of pneumococcal polysaccharide capsule during adherence and invasion of epithelial cells. Infect Immun. 2005; 73(8):4653-67. PMC: 1201225. DOI: 10.1128/IAI.73.8.4653-4667.2005. View

18.

Domon H, Nagai K, Maekawa T, Oda M, Yonezawa D, Takeda W . Neutrophil Elastase Subverts the Immune Response by Cleaving Toll-Like Receptors and Cytokines in Pneumococcal Pneumonia. Front Immunol. 2018; 9:732. PMC: 5996908. DOI: 10.3389/fimmu.2018.00732. View

19.

Cockeran R, Theron A, Steel H, Matlola N, Mitchell T, Feldman C . Proinflammatory interactions of pneumolysin with human neutrophils. J Infect Dis. 2001; 183(4):604-11. DOI: 10.1086/318536. View

20.

Kadioglu A, Andrew P . The innate immune response to pneumococcal lung infection: the untold story. Trends Immunol. 2004; 25(3):143-9. DOI: 10.1016/j.it.2003.12.006. View