Fc-engineered antibodies promote neutrophil-dependent control of Mycobacterium tuberculosis.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
22 Aug 2024
22 Aug 2024
Historique:
received:
27
04
2022
accepted:
09
07
2024
medline:
23
8
2024
pubmed:
23
8
2024
entrez:
22
8
2024
Statut:
aheadofprint
Résumé
Mounting evidence indicates that antibodies can contribute towards control of tuberculosis (TB). However, the underlying mechanisms of humoral immune protection and whether antibodies can be exploited in therapeutic strategies to combat TB are relatively understudied. Here we engineered the receptor-binding Fc (fragment crystallizable) region of an antibody recognizing the Mycobacterium tuberculosis (Mtb) capsule, to define antibody Fc-mediated mechanism(s) of Mtb restriction. We generated 52 Fc variants that either promote or inhibit specific antibody effector functions, rationally building antibodies with enhanced capacity to promote Mtb restriction in a human whole-blood model of infection. While there is likely no singular Fc profile that universally drives control of Mtb, here we found that several Fc-engineered antibodies drove Mtb restriction in a neutrophil-dependent manner. Single-cell RNA sequencing analysis showed that a restrictive Fc-engineered antibody promoted neutrophil survival and expression of cell-intrinsic antimicrobial programs. These data show the potential of Fc-engineered antibodies as therapeutics able to harness the protective functions of neutrophils to promote control of TB.
Identifiants
pubmed: 39174703
doi: 10.1038/s41564-024-01777-9
pii: 10.1038/s41564-024-01777-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : OPP1156795
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : OPP1156795
Organisme : NIAID NIH HHS
ID : 75N93019C00071
Pays : United States
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : AI150171-01
Organisme : NIAID NIH HHS
ID : 75N93019C00071
Pays : United States
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : R01A1022553
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : U54CA225088
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : U2CCA233262
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : U2CCA233280
Organisme : NIAID NIH HHS
ID : 75N93019C00071
Pays : United States
Informations de copyright
© 2024. The Author(s).
Références
Global Tuberculosis Report (World Health Organization, 2023).
Caruso, A. M. et al. Mice deficient in CD4 T cells have only transiently diminished levels of IFN-gamma, yet succumb to tuberculosis. J. Immunol. 162, 5407–5416 (1999).
pubmed: 10228018
doi: 10.4049/jimmunol.162.9.5407
Lin, P. L. et al. CD4 T cell depletion exacerbates acute Mycobacterium tuberculosis while reactivation of latent infection is dependent on severity of tissue depletion in cynomolgus macaques. AIDS Res. Hum. Retroviruses 28, 1693–1702 (2012).
pubmed: 22480184
pmcid: 3505050
doi: 10.1089/aid.2012.0028
Diedrich, C. R. et al. Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load. PLoS ONE 5, e9611 (2010).
pubmed: 20224771
pmcid: 2835744
doi: 10.1371/journal.pone.0009611
Maglione, P. J., Xu, J. & Chan, J. B cells moderate inflammatory progression and enhance bacterial containment upon pulmonary challenge with Mycobacterium tuberculosis. J. Immunol. 178, 7222–7234 (2007).
pubmed: 17513771
doi: 10.4049/jimmunol.178.11.7222
Hamasur, B. et al. A mycobacterial lipoarabinomannan specific monoclonal antibody and its F(ab’) fragment prolong survival of mice infected with Mycobacterium tuberculosis. Clin. Exp. Immunol. 138, 30–38 (2004).
pubmed: 15373902
pmcid: 1809178
doi: 10.1111/j.1365-2249.2004.02593.x
Teitelbaum, R. et al. A mAb recognizing a surface antigen of Mycobacterium tuberculosis enhances host survival. Proc. Natl Acad. Sci. USA 95, 15688–15693 (1998).
pubmed: 9861031
pmcid: 28105
doi: 10.1073/pnas.95.26.15688
Pethe, K. et al. The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature 412, 190–194 (2001).
pubmed: 11449276
doi: 10.1038/35084083
Balu, S. et al. A novel human IgA monoclonal antibody protects against tuberculosis. J. Immunol. 186, 3113–3119 (2011).
pubmed: 21257971
doi: 10.4049/jimmunol.1003189
Watson, A. et al. Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis. Nat. Commun. 12, 602 (2021).
pubmed: 33504803
pmcid: 7840946
doi: 10.1038/s41467-021-20930-0
Li, H. et al. Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 114, 5023–5028 (2017).
pubmed: 28438994
pmcid: 5441709
doi: 10.1073/pnas.1611776114
Chen, T. et al. Capsular glycan recognition provides antibody-mediated immunity against tuberculosis. J. Clin. Invest. 130, 1808–1822 (2020).
pubmed: 31935198
pmcid: 7108924
doi: 10.1172/JCI128459
Krishnananthasivam, S. et al. An anti-LpqH human monoclonal antibody from an asymptomatic individual mediates protection against Mycobacterium tuberculosis. npj Vaccines 8, 127 (2023).
pubmed: 37626082
pmcid: 10457302
doi: 10.1038/s41541-023-00710-1
Chen, T. et al. Association of human antibodies to arabinomannan with enhanced mycobacterial opsonophagocytosis and intracellular growth reduction. J. Infect. Dis. 214, 300–310 (2016).
pubmed: 27056953
pmcid: 4918826
doi: 10.1093/infdis/jiw141
Prados-Rosales, R. et al. Enhanced control of Mycobacterium tuberculosis extrapulmonary dissemination in mice by an arabinomannan–protein conjugate vaccine. PLoS Pathog. 13, e1006250 (2017).
pubmed: 28278283
pmcid: 5360349
doi: 10.1371/journal.ppat.1006250
Maglione, P. J., Xu, J., Casadevall, A. & Chan, J. Fc gamma receptors regulate immune activation and susceptibility during Mycobacterium tuberculosis infection. J. Immunol. 180, 3329–3338 (2008).
pubmed: 18292558
doi: 10.4049/jimmunol.180.5.3329
Lu, L. L. et al. A functional role for antibodies in tuberculosis. Cell 167, 433–443.e14 (2016).
pubmed: 27667685
pmcid: 5526202
doi: 10.1016/j.cell.2016.08.072
Sani, M. et al. Direct visualization by cryo-EM of the mycobacterial capsular layer: a labile structure containing ESX-1-secreted proteins. PLoS Pathog. 6, e1000794 (2010).
pubmed: 20221442
pmcid: 2832766
doi: 10.1371/journal.ppat.1000794
Lemassu, A. & Daffé, M. Structural features of the exocellular polysaccharides of Mycobacterium tuberculosis. Biochem. J. 297, 351–357 (1994).
pubmed: 8297342
pmcid: 1137836
doi: 10.1042/bj2970351
Ortalo-Magné, A. et al. Molecular composition of the outermost capsular material of the tubercle bacillus. Microbiology 141, 1609–1620 (1995).
pubmed: 7551029
doi: 10.1099/13500872-141-7-1609
Schwebach, J. R. et al. Glucan is a component of the Mycobacterium tuberculosis surface that is expressed in vitro and in vivo. Infect. Immun. 70, 2566–2575 (2002).
pubmed: 11953397
pmcid: 127896
doi: 10.1128/IAI.70.5.2566-2575.2002
Keitel, W. A. et al. Effects of infection and disease with Mycobacterium tuberculosis on serum antibody to glucan and arabinomannan: two surface polysaccharides of this pathogen. BMC Infect. Dis. 13, 276 (2013).
pubmed: 23783070
pmcid: 3722012
doi: 10.1186/1471-2334-13-276
Yu, X. et al. Comparative evaluation of profiles of antibodies to mycobacterial capsular polysaccharides in tuberculosis patients and controls stratified by HIV status. Clin. Vaccine Immunol. 19, 198–208 (2012).
pubmed: 22169090
pmcid: 3272928
doi: 10.1128/CVI.05550-11
Martin, C. J. et al. Efferocytosis is an innate antibacterial mechanism. Cell Host Microbe 12, 289–300 (2012).
pubmed: 22980326
pmcid: 3517204
doi: 10.1016/j.chom.2012.06.010
Andreu, N. et al. Optimisation of bioluminescent reporters for use with mycobacteria. PLoS ONE 5, e10777 (2010).
pubmed: 20520722
pmcid: 2875389
doi: 10.1371/journal.pone.0010777
Gunn, B. M. et al. A Fc engineering approach to define functional humoral correlates of immunity against Ebola virus. Immunity 54, 815–828.e5 (2021).
pubmed: 33852832
pmcid: 8111768
doi: 10.1016/j.immuni.2021.03.009
Smith, P., DiLillo, D. J., Bournazos, S., Li, F. & Ravetch, J. V. Mouse model recapitulating human Fcγ receptor structural and functional diversity. Proc. Natl Acad. Sci. USA 109, 6181–6186 (2012).
pubmed: 22474370
pmcid: 3341029
doi: 10.1073/pnas.1203954109
Shields, R. L. et al. High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J. Biol. Chem. 276, 6591–6604 (2001).
pubmed: 11096108
doi: 10.1074/jbc.M009483200
Lazar, G. A. et al. Engineered antibody Fc variants with enhanced effector function. Proc. Natl Acad. Sci. USA 103, 4005–4010 (2006).
pubmed: 16537476
pmcid: 1389705
doi: 10.1073/pnas.0508123103
Idusogie, E. E. et al. Engineered antibodies with increased activity to recruit complement. J. Immunol. 166, 2571–2575 (2001).
pubmed: 11160318
doi: 10.4049/jimmunol.166.4.2571
Moore, G. L., Chen, H., Karki, S. & Lazar, G. A. Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. MAbs 2, 181–189 (2010).
pubmed: 20150767
pmcid: 2840237
doi: 10.4161/mabs.2.2.11158
Richards, J. O. et al. Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells. Mol. Cancer Ther. 7, 2517–2527 (2008).
pubmed: 18723496
doi: 10.1158/1535-7163.MCT-08-0201
Masuda, K. et al. Enhanced binding affinity for FcgammaRIIIa of fucose-negative antibody is sufficient to induce maximal antibody-dependent cellular cytotoxicity. Mol. Immunol. 44, 3122–3131 (2007).
pubmed: 17379311
doi: 10.1016/j.molimm.2007.02.005
Stapleton, N. M. et al. Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential. Nat. Commun. 2, 599 (2011).
pubmed: 22186895
doi: 10.1038/ncomms1608
Tao, M. H. & Morrison, S. L. Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. J. Immunol. 143, 2595–2601 (1989).
pubmed: 2507634
doi: 10.4049/jimmunol.143.8.2595
Walker, M. R., Lund, J., Thompson, K. M. & Jefferis, R. Aglycosylation of human IgG1 and IgG3 monoclonal antibodies can eliminate recognition by human cells expressing Fc gamma RI and/or Fc gamma RII receptors. Biochem. J 259, 347–353 (1989).
pubmed: 2524188
pmcid: 1138517
doi: 10.1042/bj2590347
Zalevsky, J. et al. Enhanced antibody half-life improves in vivo activity. Nat. Biotechnol. 28, 157–159 (2010).
pubmed: 20081867
pmcid: 2855492
doi: 10.1038/nbt.1601
Dall’Acqua, W. F. et al. Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences. J. Immunol. 169, 5171–5180 (2002).
pubmed: 12391234
doi: 10.4049/jimmunol.169.9.5171
Vogel, C.-W., Fritzinger, D. C., Hew, B. E., Thorne, M. & Bammert, H. Recombinant cobra venom factor. Mol. Immunol. 41, 191–199 (2004).
pubmed: 15159065
doi: 10.1016/j.molimm.2004.03.011
Kroon, E. E. et al. Neutrophils: innate effectors of TB resistance? Front. Immunol. 9, 2637 (2018).
pubmed: 30487797
pmcid: 6246713
doi: 10.3389/fimmu.2018.02637
Lowe, D. M., Redford, P. S., Wilkinson, R. J., O’Garra, A. & Martineau, A. R. Neutrophils in tuberculosis: friend or foe? Trends Immunol. 33, 14–25 (2012).
pubmed: 22094048
doi: 10.1016/j.it.2011.10.003
Eruslanov, E. B. et al. Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice. Infect. Immun. 73, 1744–1753 (2005).
pubmed: 15731075
pmcid: 1064912
doi: 10.1128/IAI.73.3.1744-1753.2005
Dallenga, T. & Schaible, U. E. Neutrophils in tuberculosis—first line of defence or booster of disease and targets for host-directed therapy? Pathog. Dis. 74, ftw012 (2016).
pubmed: 26903072
doi: 10.1093/femspd/ftw012
Lowe, D. M. et al. Differential effect of viable versus necrotic neutrophils on Mycobacterium tuberculosis growth and cytokine induction in whole blood. Front. Immunol. 9, 903 (2018).
pubmed: 29755473
pmcid: 5934482
doi: 10.3389/fimmu.2018.00903
Baranger, K., Zani, M.-L., Chandenier, J., Dallet-Choisy, S. & Moreau, T. The antibacterial and antifungal properties of trappin-2 (pre-elafin) do not depend on its protease inhibitory function. FEBS J. 275, 2008–2020 (2008).
pubmed: 18341586
doi: 10.1111/j.1742-4658.2008.06355.x
Bellemare, A., Vernoux, N., Morin, S., Gagné, S. M. & Bourbonnais, Y. Structural and antimicrobial properties of human pre-elafin/trappin-2 and derived peptides against Pseudomonas aeruginosa. BMC Microbiol. 10, 253 (2010).
pubmed: 20932308
pmcid: 2958999
doi: 10.1186/1471-2180-10-253
Mesquita, G. et al. H-Ferritin is essential for macrophages’ capacity to store or detoxify exogenously added iron. Sci. Rep. 10, 3061 (2020).
pubmed: 32080266
pmcid: 7033252
doi: 10.1038/s41598-020-59898-0
Sanchez-Niño, M. D. et al. BASP1 promotes apoptosis in diabetic nephropathy. J. Am. Soc. Nephrol. 21, 610–621 (2010).
pubmed: 20110383
pmcid: 2844309
doi: 10.1681/ASN.2009020227
Carpenter, B. et al. BASP1 is a transcriptional cosuppressor for the Wilms’ tumor suppressor protein WT1. Mol. Cell. Biol. 24, 537–549 (2004).
pubmed: 14701728
pmcid: 343806
doi: 10.1128/MCB.24.2.537-549.2004
Waldera-Lupa, D. M. et al. Proteome-wide analysis reveals an age-associated cellular phenotype of in situ aged human fibroblasts. Aging 6, 856–878 (2014).
pubmed: 25411231
pmcid: 4247387
doi: 10.18632/aging.100698
Amulic, B., Cazalet, C., Hayes, G. L., Metzler, K. D. & Zychlinsky, A. Neutrophil function: from mechanisms to disease. Annu. Rev. Immunol. 30, 459–489 (2012).
pubmed: 22224774
doi: 10.1146/annurev-immunol-020711-074942
Nordenfelt, P. & Tapper, H. Phagosome dynamics during phagocytosis by neutrophils. J. Leukoc. Biol. 90, 271–284 (2011).
pubmed: 21504950
doi: 10.1189/jlb.0810457
Boelaert, J. R., Vandecasteele, S. J., Appelberg, R. & Gordeuk, V. R. The effect of the host’s iron status on tuberculosis. J. Infect. Dis. 195, 1745–1753 (2007).
pubmed: 17492589
doi: 10.1086/518040
Tran, A. C. et al. Mucosal therapy of multi-drug resistant tuberculosis with IgA and interferon-γ. Front. Immunol. 11, 582833 (2020).
pubmed: 33193394
pmcid: 7606302
doi: 10.3389/fimmu.2020.582833
Zimmermann, N. et al. Human isotype-dependent inhibitory antibody responses against Mycobacterium tuberculosis. EMBO Mol. Med. 8, 1325–1339 (2016).
pubmed: 27729388
pmcid: 5090662
doi: 10.15252/emmm.201606330
Irvine, E. B. et al. Robust IgM responses following intravenous vaccination with Bacille Calmette-Guérin associate with prevention of Mycobacterium tuberculosis infection in macaques. Nat. Immunol. 22, 1515–1523 (2021).
pubmed: 34811542
pmcid: 8642241
doi: 10.1038/s41590-021-01066-1
Xu, D. et al. In vitro characterization of five humanized OKT3 effector function variant antibodies. Cell. Immunol. 200, 16–26 (2000).
pubmed: 10716879
doi: 10.1006/cimm.2000.1617
Kimmey, J. M. et al. Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection. Nature 528, 565–569 (2015).
pubmed: 26649827
pmcid: 4842313
doi: 10.1038/nature16451
Moreira-Teixeira, L. et al. Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis. Nat. Commun. 11, 5566 (2020).
pubmed: 33149141
pmcid: 7643080
doi: 10.1038/s41467-020-19412-6
Lu, L. L. et al. Antibody Fc glycosylation discriminates between latent and active tuberculosis. J. Infect. Dis. 222, 2093–2102 (2020).
pubmed: 32060529
pmcid: 7661770
doi: 10.1093/infdis/jiz643
Zhang, X., Majlessi, L., Deriaud, E., Leclerc, C. & Lo-Man, R. Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. Immunity 31, 761–771 (2009).
pubmed: 19913447
doi: 10.1016/j.immuni.2009.09.016
Engler, C. & Marillonnet, S. Golden Gate cloning. Methods Mol. Biol. 1116, 119–131 (2014).
pubmed: 24395361
doi: 10.1007/978-1-62703-764-8_9
Fang, J. et al. Stable antibody expression at therapeutic levels using the 2A peptide. Nat. Biotechnol. 23, 584–590 (2005).
pubmed: 15834403
doi: 10.1038/nbt1087
Ackerman, M. E. et al. A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples. J. Immunol. Methods 366, 8–19 (2011).
pubmed: 21192942
doi: 10.1016/j.jim.2010.12.016
Karsten, C. B. et al. A versatile high-throughput assay to characterize antibody-mediated neutrophil phagocytosis. J. Immunol. Methods 471, 46–56 (2019).
pubmed: 31132351
pmcid: 6620195
doi: 10.1016/j.jim.2019.05.006
Fischinger, S. et al. A high-throughput, bead-based, antigen-specific assay to assess the ability of antibodies to induce complement activation. J. Immunol. Methods 473, 112630 (2019).
pubmed: 31301278
pmcid: 6722412
doi: 10.1016/j.jim.2019.07.002
Swartz, R. P., Naai, D., Vogel, C. W. & Yeager, H. Jr. Differences in uptake of mycobacteria by human monocytes: a role for complement. Infect. Immun. 56, 2223–2227 (1988).
pubmed: 3137162
pmcid: 259553
doi: 10.1128/iai.56.9.2223-2227.1988
McGinnis, C. S. et al. MULTI-seq: sample multiplexing for single-cell RNA sequencing using lipid-tagged indices. Nat. Methods 16, 619–626 (2019).
pubmed: 31209384
pmcid: 6837808
doi: 10.1038/s41592-019-0433-8
Chen, E. Y. et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 14, 128 (2013).
pubmed: 23586463
pmcid: 3637064
doi: 10.1186/1471-2105-14-128
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. 57, 289–300 (1995).
doi: 10.1111/j.2517-6161.1995.tb02031.x
Irvine, E. B. eirvine94/tb_fc_engineering_manuscript: release v1.0. Zenodo https://doi.org/10.5281/zenodo.11282075 (2024).
Asokan, M. et al. Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody. Proc. Natl Acad. Sci. USA 117, 18754–18763 (2020).
pubmed: 32690707
pmcid: 7414046
doi: 10.1073/pnas.2008236117
Petkova, S. B. et al. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int. Immunol. 18, 1759–1769 (2006).
pubmed: 17077181
doi: 10.1093/intimm/dxl110
Hinton, P. R. et al. Engineered human IgG antibodies with longer serum half-lives in primates. J. Biol. Chem. 279, 6213–6216 (2004).
pubmed: 14699147
doi: 10.1074/jbc.C300470200
Grevys, A. et al. Fc Engineering of human IgG1 for altered binding to the neonatal Fc receptor affects Fc effector functions. J. Immunol. 194, 5497–5508 (2015).
pubmed: 25904551
pmcid: 4432726
doi: 10.4049/jimmunol.1401218
Datta-Mannan, A. et al. Humanized IgG1 variants with differential binding properties to the neonatal Fc receptor: relationship to pharmacokinetics in mice and primates. Drug Metab. Dispos. 35, 86–94 (2007).
pubmed: 17050651
doi: 10.1124/dmd.106.011734
Yeung, Y. A. et al. Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates. J. Immunol. 182, 7663–7671 (2009).
pubmed: 19494290
doi: 10.4049/jimmunol.0804182
Datta-Mannan, A., Witcher, D. R., Tang, Y., Watkins, J. & Wroblewski, V. J. Monoclonal antibody clearance. Impact of modulating the interaction of IgG with the neonatal Fc receptor. J. Biol. Chem. 282, 1709–1717 (2007).
pubmed: 17135257
doi: 10.1074/jbc.M607161200
Chu, S. Y. et al. Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcgammaRIIb with Fc-engineered antibodies. Mol. Immunol. 45, 3926–3933 (2008).
pubmed: 18691763
doi: 10.1016/j.molimm.2008.06.027
Diebolder, C. A. et al. Complement is activated by IgG hexamers assembled at the cell surface. Science 343, 1260–1263 (2014).
pubmed: 24626930
pmcid: 4250092
doi: 10.1126/science.1248943
Wirt, T. et al. An Fc double-engineered CD20 antibody with enhanced ability to trigger complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. Transfus. Med. Hemother. 44, 292–300 (2017).
pubmed: 29070974
pmcid: 5649312
doi: 10.1159/000479978