Evidence map›Paper›PMID 39174703›Full record

ArticleNature microbiology2024

Fc-engineered antibodies promote neutrophil-dependent control of Mycobacterium tuberculosis.

Edward B Irvine, Angel Nikolov, Mehak Z Khan, Joshua M Peters, Richard Lu, Jaimie Sixsmith, Aaron Wallace, Esther van Woudenbergh, Sally Shin, Wiktor Karpinski and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  2. Review
  3. Article
  4. Review
  5. CD8Nature communications · 2026
    Article
  6. Review
  7. Review
  8. A proteome-wide atlas of humoral immunity toFrontiers in immunology · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. c-Myc inhibits macrophage antimycobacterial response inbioRxiv : the preprint server for biology · 2025
    Article
  16. Article
  17. Review
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Edward B IrvineRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Angel NikolovRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Mehak Z KhanRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Joshua M PetersRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Richard LuRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Jaimie SixsmithDepartment of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Aaron WallaceMassBiologics of the University of Massachusetts Chan Medical School, Boston, MA, USA.
Esther van WoudenberghRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7363-6649
Sally ShinRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Wiktor KarpinskiRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Jeff C HsiaoRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0800-9977
Arturo CasadevallDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-9402-9167
Bryan D BrysonRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1716-6712
Lisa CavaciniMassBiologics of the University of Massachusetts Chan Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1417-8339
Patricia S GraceRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Galit Alter *Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. galit.alter@modernatx.com.ORCID http://orcid.org/0000-0002-7680-9215
Sarah M Fortune *Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. sfortune@hsph.harvard.edu.ORCID http://orcid.org/0000-0001-7565-9975

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI RAJESH T GANDHI · 2004 to 2026
$94.4M
IMMUNE MECHANISMS OF PROTECTION AGAINST MYCOBACTERIUM TUBERCULOSIS CENTER (IMPAC-TB)75N93019C00071 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI FORTUNE, SARAH · 2019 to 2025
$57.3M
Molecular Analysis of the Host Immune Response in LeprosyR01AI022553 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERT L MODLIN · 1989 to 2026
$15.7M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2018 to 2022
$10.8M
Omic and Multidimensional Spatial Atlas of Metastatic Breast CancerU2CCA233280 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI GOECKS, JEREMY · 2018 to 2023
$9.7M
Pre-cancer atlases of cutaneous and hematologic origin (PATCH Center)U2CCA233262 · NCI · HARVARD MEDICAL SCHOOL · PI SANTAGATA, SANDRO · 2018 to 2023
$8.7M
Dynamics of the cellular and molecular architecture of human pulmonary TB granulomasR01AI166313 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROBERT L MODLIN · 2022 to 2026
$3.2M
Exploiting Fc-engineering to dissect mechanisms of anti-microbial action of M. tuberculosis-specific antibodiesF31AI150171 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI IRVINE, EDWARD BUFORD · 2020 to 2021
$64k
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) OPP1156795Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) AI150171-01Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01A1022553Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U2CCA233262Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U2CCA233280Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U54CA225088NCI NIH HHS U2C CA233262NCI NIH HHS U2C CA233280NCI NIH HHS U54 CA225088NIAID NIH HHS 75N93019C00071NIAID NIH HHS F31 AI150171NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI022553NIAID NIH HHS R01 AI166313
6 · The paper itself

Abstract

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.

Indexed as

Antibodies, BacterialImmunoglobulin Fc FragmentsMycobacterium tuberculosisNeutrophilsTuberculosisAnimalsHumansMiceProtein EngineeringReceptors, FcAntibodies, BacterialImmunoglobulin Fc FragmentsReceptors, Fc

Identifiers

PMID39174703
PMCPMC11371646

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.