The Annexin A1/FPR2 pathway controls the inflammatory response and bacterial dissemination in experimental pneumococcal pneumonia.
Animals
Annexin A1
/ metabolism
Disease Models, Animal
Inflammation
/ metabolism
Macrophages
/ metabolism
Male
Mice, Inbred BALB C
Mice, Inbred C57BL
Neutrophils
/ metabolism
Phagocytosis
/ drug effects
Pneumonia, Pneumococcal
/ metabolism
Receptors, Formyl Peptide
/ metabolism
Receptors, Lipoxin
/ metabolism
Streptococcus pneumoniae
/ metabolism
Streptococcus pneumoniae
inflammation
pro-resolving mediator
resolution
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
30
08
2019
revised:
29
11
2019
accepted:
09
12
2019
pubmed:
8
1
2020
medline:
30
9
2020
entrez:
8
1
2020
Statut:
ppublish
Résumé
Streptococcus pneumoniae is a major cause of community-acquired pneumonia leading to high mortality rates. Inflammation triggered by pneumococcal infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Annexin A1 (AnxA1) mainly acts through Formyl Peptide Receptor 2 (FPR2) inducing the resolution of inflammation. Here, we have evaluated the role of AnxA1 and FPR2 during pneumococcal pneumonia in mice. For that, AnxA1, Fpr2/3 knockout (KO) mice and wild-type (WT) controls were infected intranasally with S pneumoniae. AnxA1 and Fpr2/3 KO mice were highly susceptible to infection, displaying uncontrolled inflammation, increased bacterial dissemination, and pulmonary dysfunction compared to WT animals. Mechanistically, the absence of AnxA1 resulted in the loss of lung barrier integrity and increased neutrophil activation upon S pneumoniae stimulation. Importantly, treatment of WT or AnxA1 KO-infected mice with Ac2-26 decreased inflammation, lung damage, and bacterial burden in the airways by increasing macrophage phagocytosis. Conversely, Ac2-26 peptide was ineffective to afford protection in Fpr2/3 KO mice during infection. Altogether, these findings show that AnxA1, via FPR2, controls inflammation and bacterial dissemination during pneumococcal pneumonia by promoting host defenses, suggesting AnxA1-based peptides as a novel therapeutic strategy to control pneumococcal pneumonia.
Identifiants
pubmed: 31908042
doi: 10.1096/fj.201902172R
doi:
Substances chimiques
Annexin A1
0
Receptors, Formyl Peptide
0
Receptors, Lipoxin
0
annexin A1, mouse
0
formyl peptide receptor 2, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2749-2764Informations de copyright
© 2019 Federation of American Societies for Experimental Biology.
Références
Martens P, Worm SW, Lundgren B, Konradsen HB, Benfield T. Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited. BMC Infect Dis. 2004;4:21-28.
Choi EH, Zhang F, Lu Y-J, Malley R. Capsular polysaccharide (CPS) release by serotype 3 pneumococcal strains reduces the protective effect of anti-type 3 CPS antibodies. Clin Vaccine Immunol. 2015;23:162-167.
Tavares LP, Garcia CC, Vago JP, et al. Inhibition of PDE4 during pneumococcal pneumonia reduces inflammation and lung injury in mice. Am J Respir Cell Mol Biol. 2015;55:24-34.
Nie W, Zhang Y, Cheng J, Xiu Q. Corticosteroids in the treatment of community-acquired pneumonia in adults: a meta-analysis. PLoS ONE. 2012;7:e47926.
Craig A, Mai J, Cai S, Jeyaseelan S. Neutrophil recruitment to the lungs during bacterial pneumonia. Infect Immun. 2009;77:568-575.
Hussell T, Bell TJ. Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol. 2014;14:81-93.
Dockrell DH, Whyte MKB, Mitchell TJ. Pneumococcal pneumonia mechanisms of infection and resolution. Chest. 2012;142:482-491.
Levy BD, Serhan CN. Resolution of acute inflammation in the lung. Annu Rev Physiol. 2014;76:467-492.
Tavares LP, Garcia CC, Machado MG, et al. CXCR1/2 antagonism is protective during influenza and post-influenza pneumococcal infection. Front Immunol. 2017;8:1799-1813.
Wang H, Anthony D, Yatmaz S, et al. Aspirin-triggered resolvin D1 reduces pneumococcal lung infection and inflammation in a viral and bacterial coinfection pneumonia model. Clin Sci. 2017;131:2347-2362.
Basil MC, Levy BD. Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol. 2016;16:51-67.
Dalli J. Does promoting resolution instead of inhibiting inflammation represent the new paradigm in treating infections? Mol Aspects Med. 2017;58:1-9.
Serhan CN. Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms. FASEB J. 2017;31:1273-1288.
Vago JP, Nogueira CRC, Tavares LP, et al. Annexin A1 modulates natural and glucocorticoid-induced resolution of inflammation by enhancing neutrophil apoptosis. J Leukoc Biol. 2012;92:249-258.
Maderna P, Yona S, Perretti M, Godson C. Modulation of phagocytosis of apoptotic neutrophils by supernatant from dexamethasone-treated macrophages and annexin-derived peptide Ac(2-26). J Immunol. 2005;174:3727-3733.
Sugimoto MA, Vago JP, Perretti M, Teixeira MM. Mediators of the resolution of the inflammatory response. Trends Immunol. 2019;40:212-227.
Damazo AS, Yona S, Flower RJ, Perretti M, Oliani SM. Spatial and temporal profiles for anti-inflammatory gene expression in leukocytes during a resolving model of peritonitis. J Immunol. 2006;176:4410-4418.
Liao W-I, Wu S-Y, Wu G-C, et al. Ac2-26, an annexin A1 peptide, attenuates ischemia-reperfusion-induced acute lung injury. Int J Mol Sci. 2017;18:2-26.
Gavins FNE, Hughes EL, Buss NAPS, Holloway PM, Getting SJ, Buckingham JC. Leukocyte recruitment in the brain in sepsis: involvement of the annexin 1-FPR2/ALX anti-inflammatory system. FASEB J. 2012;26:4977-4989.
Girol AP, Mimura KKO, Drewes CC, et al. Anti-inflammatory mechanisms of the annexin A1 protein and its mimetic peptide Ac2-26 in models of ocular inflammation in vivo and in vitro. J Immunol. 2013;190:5689-5701.
Hannon R, Croxtall JD, Getting SJ, et al. Aberrant inflammation and resistance to glucocorticoids in Annexin 1-/- Mouse. FASEB J. 2003;17:253-255.
Vanessa KHQ, Julia MG, Wenwei L, et al. Absence of Annexin A1 impairs host adaptive immunity against Mycobacterium tuberculosis in vivo. Immunobiology. 2015;220:614-623.
Gobbetti T, Coldewey SM, Chen J, et al. Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis. Proc Natl Acad Sci U S A. 2014;111:18685-18690.
Cooray SN, Gobbetti T, Montero-Melendez T, et al. Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2 determines proresolving functional responses. Proc Natl Acad Sci U S A. 2013;110:18232-18237.
Corminboeuf O, Leroy X. FPR2/ALXR agonists and the resolution of inflammation. J Med Chem. 2015;58:537-559.
Li Y, Cai L, Wang H, et al. Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2. Oncogene. 2011;30:3887-3899.
Dufton N, Hannon R, Brancaleone V, et al. Anti-inflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation. J Immunol. 2010;184:2611-2619.
Lastrucci C, Baillif V, Behar A, et al. Molecular and cellular profiles of the resolution phase in a damage-associated molecular pattern (DAMP)-mediated peritonitis model and revelation of leukocyte persistence in peritoneal tissues. FASEB J. 2015;29:1914-1929.
Scalerandi MV, Peinetti N, Leimgruber C, et al. Inefficient N2-like neutrophils are promoted by androgens during infection. Front Immunol; 2018:9:1980-1994.
Yao Y, Jeyanathan M, Haddadi S, et al. Induction of autonomous memory alveolar macrophages requires T cell help and is critical to trained immunity. Cell. 2018;175:1634-1650.e17.
Marriott HM, Jackson LE, Wilkinson TS, et al. Reactive oxygen species regulate neutrophil recruitment and survival in pneumococcal pneumonia. Am J Respir Crit Care Med. 2008;177:887-895.
Yona S, Heinsbroek SEM, Peiser L, Gordon S, Perretti M, Flower RJ. Impaired phagocytic mechanism in annexin 1 null macrophages. Br J Pharmacol. 2006;148:469-477.
Patel DM, Ahmad SF, Weiss DG, Gerke V, Kuznetsov SA. Annexin A1 is a new functional linker between actin filaments and phagosomes during phagocytosis. J Cell Sci. 2011;124:578-588.
Steel HC, Cockeran R, Anderson R, Feldman C. Overview of community-acquired pneumonia and the role of inflammatory mechanisms in the immunopathogenesis of severe pneumococcal disease. Mediators Inflamm. 2013;2013:490346.
Fullerton JN, Gilroy DW. Resolution of inflammation: a new therapeutic frontier. Nat Rev Drug Discov. 2016;15:551-567.
Garcia CC, Guabiraba R, Soriani FM, Teixeira MM. The development of anti-inflammatory drugs for infectious diseases. Discov Med. 2010;10:479-488.
Leoni G, Nusrat A. Annexin A1: shifting the balance towards resolution and repair. Biol Chem. 2016;397:971-979.
Babbin BA, Laukoetter MG, Nava P, et al. Annexin A1 regulates intestinal mucosal injury, inflammation, and repair. J Immunol. 2008;181:5035-5044.
Senthilkumaran C, Clark ME, Abdelaziz K, et al. Increased annexin A1 and A2 levels in bronchoalveolar lavage fluid are associated with resistance to respiratory disease in beef calves. Vet Res. 2013;44:24-32.
Light RB. Pulmonary pathophysiology of pneumococcal pneumonia. Semin Respir Infect. 1999;14:218-226.
Yang YH, Morand EF, Getting SJ, et al. Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen-induced arthritis. Arthritis Rheum. 2004;50:976-984.
Galvão I, Vago JP, Barroso LC, et al. Annexin A1 promotes timely resolution of inflammation in murine gout. Eur J Immunol. 2017;47:585-596.
Perretti M, Solito E. Annexin 1 and neutrophil apoptosis. Biochem Soc Trans. 2004;32:507-510.
Damazo AS, Yona S, D’Acquisto F, Flower RJ, Oliani SM, Perretti M. Critical protective role for annexin 1 gene expression in the endotoxemic murine microcirculation. Am J Pathol. 2005;166:1607-1617.
Zhang Z, Huang L, Zhao W, Rigas B. Annexin 1 induced by anti-inflammatory drugs binds to NF-kappaB and inhibits its activation: anticancer effects in vitro and in vivo. Cancer Res. 2010;70:2379-2388.
Meduri GU. Clinical review: a paradigm shift: the bidirectional effect of inflammation on bacterial growth. Clinical implications for patients with acute respiratory distress syndrome. Crit Care. 2002;6:24-29.
van der Poll T, Marchant A, Keogh CV, Goldman M, Lowry SF. Interleukin-10 impairs host defense in murine pneumococcal pneumonia. J Infect Dis. 1996;174:994-1000.
Fica A, Bunster N, Aliaga F, Olivares F, Porte L, Braun S, et al. Bacteremic pneumococcal pneumonia: serotype distribution, antimicrobial susceptibility, severity scores, risk factors, and mortality in a single center in Chile. Brazilian J Infect Dis. 2014;18:115-123.
LaFemina MJ, Sutherland KM, Bentley T, et al. Claudin-18 deficiency results in alveolar barrier dysfunction and impaired alveologenesis in mice. Am J Respir Cell Mol Biol. 2014;51:550-558.
Mazzon E, Cuzzocrea S. Role of TNF-alpha in lung tight junction alteration in mouse model of acute lung inflammation. Respir Res. 2007;8:75-94.
Coyne CB, Gambling TM, Boucher RC, Carson JL, Johnson LG. Role of claudin interactions in airway tight junctional permeability. Am J Physiol Lung Cell Mol Physiol. 2003;285:1166-1178.
Leoni G, Neumann P-A, Kamaly N, et al. Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest. 2015;125:1215-1227.
Cristante E, McArthur S, Mauro C, et al. Identification of an essential endogenous regulator of blood-brain barrier integrity, and its pathological and therapeutic implications. Proc Natl Acad Sci U S A. 2013;110:832-841.
Coyne CB, Vanhook MK, Gambling TM, Carson JL, Boucher RC, Johnson LG. Regulation of airway tight junctions by proinflammatory cytokines. Mol Biol Cell. 2002;13:3218-3234.
Trentin PG, Ferreira TPT, Arantes ACS, et al. Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice. Br J Pharmacol. 2015;172:3058-3071.
Perretti M, Chiang N, La M, et al. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nat Med. 2002;8:1296-1302.
Schloer S, Hübel N, Masemann D, et al. The annexin A1/FPR2 signaling axis expands alveolar macrophages, limits viral replication, and attenuates pathogenesis in the murine influenza A virus infection model. FASEB J. 2019;33:12188-12199.