Evidence map›Paper›PMID 40449485›Full record

ArticleImmunity2025

Antibody-Fab and -Fc features promote Mycobacterium tuberculosis restriction.

Patricia S Grace, Joshua M Peters, Jaimie Sixsmith, Richard Lu, Edward B Irvine, Corinne Luedeman, Brooke A Fenderson, Andrew Vickers, Matthew D Slein, Tanya McKitrick and 17 more

Abstract read
In one paragraph

Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Article
  2. Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. A proteome-wide atlas of humoral immunity toFrontiers in immunology · 2026
    Article
  11. Article
  12. Review
  13. Review
  14. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Patricia S GraceRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Joshua M PetersRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jaimie SixsmithDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Richard LuRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Edward B IrvineRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Corinne LuedemanRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Brooke A FendersonRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Andrew VickersDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Matthew D SleinRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Tanya McKitrickDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Mo-Hui WeiDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Richard D CummingsDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Aaron WallaceMassBiologics of the University of Massachusetts Medical School, Boston, MA, USA.
Lisa A CavaciniMassBiologics of the University of Massachusetts Medical School, Boston, MA, USA.
Alok ChoudharyPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
Megan K ProulxDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
Christopher SundlingDivision of Infectious Diseases, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
Gunilla KälleniusDivision of Infectious Diseases, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
Rajko ReljicInstitute for Infection and Immunity, St. George's University, London, UK.
Joel D ErnstDivision of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA.
Arturo CasadevallDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Camille LochtUniversity of Lille, CNRS, Inserm, CHU Lille Institut Pasteur de Lille, U1019-URM9017_Center for Infection and Immunity of Lille, 5900 Lille, France.
Abraham PinterPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
Christopher M SassettiDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
Bryan D BrysonRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sarah M FortuneRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: sfortune@hsph.harvard.edu.
Galit AlterRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: galter@partners.org.

Funding

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
INFECTIOUS DISEASE AND BASIC MICROBIOLOGICAL MECHANISMST32AI007061 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Marcia B Goldberg · 1985 to 2026
$12.1M
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
NIAID NIH HHS 75N93019C00071NIAID NIH HHS R01 AI166313NIAID NIH HHS T32 AI007061
6 · The paper itself

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), a leading cause of death by an infectious disease globally, has no efficacious vaccine. Antibodies are implicated in M. tuberculosis control, but the mechanisms of action remain poorly understood. We assembled a library of monoclonal antibodies (mAb) and screened for M. tuberculosis-restrictive activity in mice, identifying protective antibodies targeting diverse antigens. To dissect the mechanism of mAb-mediated M. tuberculosis restriction, we optimized a protective lipoarabinomannan-specific mAb, generating Fc variants. In vivo analysis of these Fc variants revealed a role for Fc-effector function in M. tuberculosis restriction. Restrictive Fc variants altered distribution of M. tuberculosis across innate immune cells. Single-cell transcriptomics highlighted distinctly activated pathways within innate immune cell subpopulations, identifying early activation of neutrophils as a key signature of mAb-mediated M. tuberculosis restriction. Therefore, antibody-mediated restriction of M. tuberculosis is associated with reorganization of the tissue-level immune response to infection and depends on the collaboration of antibody Fab and Fc.

Indexed as

Antibodies, BacterialAntibodies, MonoclonalImmunoglobulin Fab FragmentsImmunoglobulin Fc FragmentsMycobacterium tuberculosisTuberculosisAnimalsAntigens, BacterialHumansImmunity, InnateLipopolysaccharidesMiceMice, Inbred C57BLNeutrophilsAntibodies, BacterialAntibodies, MonoclonalAntigens, BacterialImmunoglobulin Fab FragmentsImmunoglobulin Fc FragmentslipoarabinomannanLipopolysaccharidesalveolar macrophageFc effector functionhumoral immunitylung immunitymonoclonal antibodyMycobacterium tuberculosisneutrophilopsinophagocytosis

Identifiers

PMID40449485
PMCPMC12476823

What OpenQuestion holds

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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.