Leukotriene B4-induced neutrophil extracellular traps impede the clearance of Pneumocystis.
Fungal
Leukotriene B4
Lung injury
Neutrophil extracellular trap
Pneumocystis pneumonia
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
05 Mar 2024
05 Mar 2024
Historique:
revised:
02
02
2024
received:
20
09
2023
accepted:
02
02
2024
medline:
5
3
2024
pubmed:
5
3
2024
entrez:
5
3
2024
Statut:
aheadofprint
Résumé
Pneumocystis pneumonia (PCP) is a fungal pulmonary disease with high mortality in immunocompromised patients. Neutrophils are essential in defending against fungal infections; however, their role in PCP is controversial. Here we aim to investigate the effects of neutrophil extracellular traps (NETs) on Pneumocystis clearance and lung injury using a mouse model of PCP. Intriguingly, although neutrophils play a fundamental role in defending against fungal infections, NETs failed to eliminate Pneumocystis, but instead impaired the killing of Pneumocystis. Mechanically, Pneumocystis triggered Leukotriene B4 (LTB4)-dependent neutrophil swarming, leading to agglutinative NET formation. Blocking Leukotriene B4 with its receptor antagonist Etalocib significantly reduced the accumulation and NET release of neutrophils in vitro and in vivo, enhanced the killing ability of neutrophils against Pneumocystis, and alleviated lung injury in PCP mice. This study identifies the deleterious role of agglutinative NETs in Pneumocystis infection and reveals a new way to prevent NET formation, which provides new insights into the pathogenesis of PCP.
Identifiants
pubmed: 38440842
doi: 10.1002/eji.202350779
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2350779Subventions
Organisme : National Natural Science Foundation of China
ID : 82372189
Organisme : National Natural Science Foundation of China
ID : 82202415
Organisme : National Natural Science Foundation of China
ID : 82172128
Organisme : Beijing High-Level Public Health Technical Talent Training Program
ID : discipline backbone talent-02-32
Informations de copyright
© 2024 Wiley-VCH GmbH.
Références
Apostolopoulou, A. and Fishman, J.A., The pathogenesis and Diagnosis of Pneumocystis jiroveci pneumonia. J. Fungi. 2022. 8: 1167.
Azoulay, É., de Castro, N. and Barbier, F., Critically Ill Patients With HIV. Chest. 2020. 157: 293-309.
de Boer, M.G.J., Bruijnesteijn van Coppenraet, L.E.S., Gaasbeek, A., Berger, S.P., Gelinck, L.B.S., van Houwelingen, H.C., van den Broek, P., Kuijper, E.J., Kroon, F.P. and Vandenbroucke, J.P., An outbreak of Pneumocystis jiroveci pneumonia with 1 predominant genotype among renal transplant recipients: interhuman transmission or a common environmental source? Clin. Infect. Dis. 2007. 44: 1143-1149.
Liu, B., Jin, Y., Yang, J., Han, Y., Shan, H., Qiu, M., Zhao, X. et al., Extracellular vesicles from lung tissue drive bone marrow neutrophil recruitment in inflammation. J. Extracell. Vesicles. 2022. 11: e12223.
Haslett, C., Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am. J. Respir. Crit. Care Med. 1999. 160: 5-11.
Azoulay, E., Parrot, A., Flahault, A., Cesari, D., Lecomte, I., Roux, P., Saidi, F., Fartoukh, M., Bernaudin, J.F., Cadranel, J. and Mayaud, C., AIDS-related Pneumocystis carinii pneumonia in the era of adjunctive steroids: implication of BAL neutrophilia. Am. J. Respir. Crit. Care Med. 1999. 160: 493-499.
Swain, S.D., Wright, T.W., Degel, P.M., Gigliotti, F. and Harmsen, A.G., Neither neutrophils nor reactive oxygen species contribute to tissue damage during Pneumocystis pneumonia in mice. Infect. Immun. 2004. 72: 5722-5732.
Barnado, A., Crofford, L.J. and Oates, J.C., At the Bedside: Neutrophil extracellular traps (NETs) as targets for biomarkers and therapies in autoimmune diseases. J. Leukoc. Biol. 2016. 99: 265-278.
Urban, C.F., Reichard, U., Brinkmann, V. and Zychlinsky, A., Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell. Microbiol. 2006. 8: 668-676.
McCormick, A., Heesemann, L., Wagener, J., Marcos, V., Hartl, D., Loeffler, J., Heesemann, J. et al., NETs formed by human neutrophils inhibit growth of the pathogenic mold Aspergillus fumigatus. Microbes Infect. 2010. 12: 928-936.
Zhang, C., Rong, H.-M., Li, T., Zhai, K. and Tong, Z.-H., PD-1 deficiency promotes macrophage activation and T-helper cell type 1/T-helper cell type 17 response in Pneumocystis pneumonia. Am. J. Respir. Cell Mol. Biol. 2020. 62: 767-782.
Wang, C., Wei, Z., Han, Z., Wang, J., Zhang, X., Wang, Y., Liu, Q. et al., Neutrophil extracellular traps promote cadmium chloride-induced lung injury in mice. Environ. Pollut. 2019. 254: 113021.
Zhu, L., Chen, Z., Zeng, H., Li, X., Ma, Y., Duan, J., Feng, Y. et al., High levels of circulating cell-free DNA are associated with a poor prognosis in patients with severe fever with thrombocytopenia syndrome. Clin. Infect. Dis. 2020. 70: 1941-1949.
Bodogai, M., Moritoh, K., Lee-Chang, C., Hollander, C.M., Sherman-Baust, C.A., Wersto, R.P., Araki, Y. et al., Immunosuppressive and prometastatic functions of myeloid-derived suppressive cells rely upon education from tumor-associated B cells. Cancer Res. 2015. 75: 3456-3465.
Kenny, E.F., Herzig, A., Krüger, R., Muth, A., Mondal, S., Thompson, P.R., Brinkmann, V. et al., Diverse stimuli engage different neutrophil extracellular trap pathways. eLife. 2017. 6: e24437.
Hopke, A., Scherer, A., Kreuzburg, S., Abers, M.S., Zerbe, C.S., Dinauer, M.C., Mansour, M.K. et al., Neutrophil swarming delays the growth of clusters of pathogenic fungi. Nat. Commun. 2020. 11: 2031.
Li, P., Oh, D.Y., Bandyopadhyay, G., Lagakos, W.S., Talukdar, S., Osborn, O., Johnson, A. et al., LTB4 promotes insulin resistance in obese mice by acting on macrophages, hepatocytes and myocytes. Nat. Med. 2015. 21: 239-247.
Kim, N.D. and Luster, A.D., regulation of immune cells by eicosanoid receptors. Sci. World J. 2007. 7: 1307-1328.
Tager, A.M. and Luster, A.D., BLT1 and BLT2: the leukotriene B4 receptors. Prostaglandins Leukot. Essent. Fatty Acids. 2003. 69: 123-134.
Carmona, E.M., Lamont, J.D., Xue, A., Wylam, M. and Limper, A.H., Pneumocystis cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells. Respir. Res. 2010. 11: 95.
Benfield, T.L., van Steenwijk, R., Nielsen, T.L., Dichter, J.R., Lipschik, G.Y., Jensen, B.N., Junge, J., Shelhamer, J.H. and Lundgren, J.D., Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia. Respir. Med. 1995. 89: 285-290.
Benfield, T.L., Vestbo, J., Junge, J., Nielsen, T.L., Jensen, A.B. and Lundgren, J.D., Prognostic value of interleukin-8 in AIDS-associated Pneumocystis carinii pneumonia. Am. J. Respir. Crit. Care Med. 1995. 151: 1058-1062.
Villard, J., Dayer-Pastore, F., Hamacher, J., Aubert, J.D., Schlegel-Haueter, S. and Nicod, L.P., GRO alpha and interleukin-8 in Pneumocystis carinii or bacterial pneumonia and adult respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 1995. 152: 1549-1554.
Caudrillier, A., Kessenbrock, K., Gilliss, B.M., Nguyen, J.X., Marques, M.B., Monestier, M., Toy, P. et al., Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J. Clin. Invest. 2012. 122: 2661-2671.
HJ, F., DS, B., DH, C., EM, M., ML, N., BW, R., BJ, R. et al., Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme study group. N. Engl. J. Med. 1994. 331: 637-642.