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Tanner L, Bhongir RKV, Karlsson CAQ, et al. Citrullination of extracellular histone H3.1 reduces antibacterial activity and exacerbates its proteolytic degradation. J Cyst Fibros. 2020;20(2):346-355doi: 10.1016/j.jcf.2020.07.010.
Tanner, L., Bhongir, R. K. V., Karlsson, C. A. Q., Le, S., Ljungberg, J. K., Andersson, P., Andersson, C., Malmström, J., Egesten, A., & Single, A. B. (2021). Citrullination of extracellular histone H3.1 reduces antibacterial activity and exacerbates its proteolytic degradation. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 20(2), 346-355. https://doi.org/10.1016/j.jcf.2020.07.010
Tanner, Lloyd, et al. "Citrullination of extracellular histone H3.1 reduces antibacterial activity and exacerbates its proteolytic degradation." Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society vol. 20,2 (2021): 346-355. doi: https://doi.org/10.1016/j.jcf.2020.07.010
Tanner L, Bhongir RKV, Karlsson CAQ, Le S, Ljungberg JK, Andersson P, Andersson C, Malmström J, Egesten A, Single AB. Citrullination of extracellular histone H3.1 reduces antibacterial activity and exacerbates its proteolytic degradation. J Cyst Fibros. 2021 Mar;20(2):346-355. doi: 10.1016/j.jcf.2020.07.010. Epub 2020 Jul 26. PMID: 32727663.
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J Cyst Fibros. 2021 Mar;20(2):346-355. doi: 10.1016/j.jcf.2020.07.010. Epub 2020 Jul 26.

Citrullination of extracellular histone H3.1 reduces antibacterial activity and exacerbates its proteolytic degradation.

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

Lloyd Tanner, Ravi K V Bhongir, Christofer A Q Karlsson, Sandy Le, Johanna K Ljungberg, Pia Andersson, Cecilia Andersson, Johan Malmström, Arne Egesten, Andrew B Single

Affiliations

  1. Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden.
  2. Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
  3. Respiratory Cell Biology, Department of Experimental Medical Sciences Lund, Lund University, Lund, Sweden.
  4. Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden. Electronic address: [email protected].

PMID: 32727663 DOI: 10.1016/j.jcf.2020.07.010

Abstract

BACKGROUND: Cystic fibrosis (CF), involves excessive airway accumulation of neutrophils, often in parallel with severe infection caused by Pseudomonas aeruginosa. Free histones are known to possess bactericidal properties, but the degree of antibacterial activity exerted on specific lung-based pathogens is largely unknown. Neutrophils have a high content of peptidyl deiminase 4 (PADI4), which citrullinate cationic peptidyl-arginines. In histone H3.1, several positions in the NH

METHODS: Full-length and segmented histone subunit H3.1 was investigated for bactericidal activity towards P. aeruginosa (strain PAO1). PADI4-induced citrullination of histone H3.1 was assessed for antibacterial activity towards P. aeruginosa. Next, the effect of neutrophil elastase (NE)-mediated proteolysis of histone H3.1 was investigated. Finally, PADI4, H3.1, and citrullinated H3.1 were examined in healthy control and CF patient lung tissues.

RESULTS: Full-length histone H3.1 and sections of the histone H3.1 tail, displayed bactericidal activity towards P. aeruginosa. These antibacterial effects were reduced following citrullination by PADI4 or proteolysis by NE. Interestingly, citrullination of histone H3.1 exacerbated NE-mediated degradation. In CF lung tissue, citrullinated histone H3.1 and PADI4 immunoreactivity was abundant. Degraded histone H3.1 was detected in the sputum of CF patients but was absent in the sputum of healthy controls.

CONCLUSIONS: Citrullination impairs the antibacterial activity of histone H3.1 and exacerbates its proteolytic degradation by NE. Citrullination is likely to play an important role during resolution of acute inflammation. However, in chronic inflammation akin to CF, citrullination may dampen host defense and promote pathogen survival, as exemplified by P. aeruginosa.

Copyright © 2020. Published by Elsevier B.V.

Keywords: AMPs; Citrullination; Cystic fibrosis; Innate immunity; PADI4; Pseudomonas aeruginosa

Conflict of interest statement

Declaration of Competing Interest The authors declare that there are no conflicts of interest.

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