Evidence map›Paper›PMID 27355424›Full record

ArticlePLoS pathogens2016

S100A12 Is Part of the Antimicrobial Network against Mycobacterium leprae in Human Macrophages.

Susan Realegeno, Kindra M Kelly-Scumpia, Angeline Tilly Dang, Jing Lu, Rosane Teles, Philip T Liu, Mirjam Schenk, Ernest Y Lee, Nathan W Schmidt, Gerard C L Wong and 5 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% of its field
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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Meta-Analysis ofFrontiers in immunology · 2019
    Pooled it
  2. Article
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  5. Article
  6. Article
  7. IFN-γ-Driven macrophage responses in the immunity toFrontiers in cellular and infection microbiology · 2025
    Review
  8. Article
  9. Article
  10. Normalizing granuloma vasculature and matrix improves drug delivery and reduces bacterial burden in tuberculosis-infected rabbits.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Review
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  13. Review
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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

15 authors at 3 institutions in 2 countries.

Susan RealegenoDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
Kindra M Kelly-ScumpiaDivision of Dermatology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, United States of America.
Angeline Tilly DangDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
Jing LuDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California, United States of America.
Rosane TelesDivision of Dermatology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, United States of America.
Philip T LiuUCLA/Orthopedic Hospital Department of Orthopedic Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, United States of America.
Mirjam SchenkDivision of Dermatology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, United States of America.
Ernest Y LeeDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, California, United States of America.ORCID 0000-0001-5144-2552
Nathan W SchmidtDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, California, United States of America.
Gerard C L WongDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, California, United States of America.
Euzenir N SarnoLeprosy Laboratory, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Thomas H ReaDepartment of Dermatology, University of Southern California School of Medicine, Los Angeles, California, United States of America.
Maria T OchoaDepartment of Dermatology, University of Southern California School of Medicine, Los Angeles, California, United States of America.
Matteo PellegriniDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California, United States of America.
Robert L ModlinDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
University of California, Los Angeles · USUniversity of Southern California · USFundação Oswaldo Cruz · BR

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
Molecular Analysis of the Host Immune Response in LeprosyR01AI022553 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERT L MODLIN · 1989 to 2026
$15.7M
TCR GAMMA/DELTA LYMPHOCYTES IN HUMAN SKIN LESIONSR01AR040312 · NIAMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MODLIN, ROBERT L · 1990 to 2025
$10.4M
Vitamin D Metabolism in LeprosyP50AR063020 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2012 to 2016
$7.8M
Systems in Integrative BiologyT32GM008185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHOU, TOM · 1987 to 2022
$4.6M
ROLE OF TOLL-LIKE RECEPTORS IN SKINR37AI047868 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2000 to 2009
$2.9M
Divergence of Phagocytic and Antimicrobial Programs in LeprosyR01AI047868 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2010 to 2014
$2.4M
Role of Vitamin D Prohormone 25-OHD in the Immune Response to TuberculosisR01HL119068 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LIU, PHILIP T., MODLIN, ROBERT L · 2014 to 2017
$1.5M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NHLBI NIH HHS R01 HL119068NIAID NIH HHS P30 AI028697NIAID NIH HHS R01 AI022553NIAID NIH HHS R01 AI047868NIAID NIH HHS R37 AI047868NIAMS NIH HHS P50 AR063020NIAMS NIH HHS R01 AR040312NIGMS NIH HHS T32 GM008185
6 · The paper itself

Abstract

Triggering antimicrobial mechanisms in macrophages infected with intracellular pathogens, such as mycobacteria, is critical to host defense against the infection. To uncover the unique and shared antimicrobial networks induced by the innate and adaptive immune systems, gene expression profiles generated by RNA sequencing (RNAseq) from human monocyte-derived macrophages (MDMs) activated with TLR2/1 ligand (TLR2/1L) or IFN-γ were analyzed. Weighed gene correlation network analysis identified modules of genes strongly correlated with TLR2/1L or IFN-γ that were linked by the "defense response" gene ontology term. The common TLR2/1L and IFN-γ inducible human macrophage host defense network contained 16 antimicrobial response genes, including S100A12, which was one of the most highly induced genes by TLR2/1L. There is limited information on the role of S100A12 in infectious disease, leading us to test the hypothesis that S100A12 contributes to host defense against mycobacterial infection in humans. We show that S100A12 is sufficient to directly kill Mycobacterium tuberculosis and Mycobacterium leprae. We also demonstrate that S100A12 is required for TLR2/1L and IFN-γ induced antimicrobial activity against M. leprae in infected macrophages. At the site of disease in leprosy, we found that S100A12 was more strongly expressed in skin lesions from tuberculoid leprosy (T-lep), the self-limiting form of the disease, compared to lepromatous leprosy (L-lep), the progressive form of the disease. These data suggest that S100A12 is part of an innate and adaptive inducible antimicrobial network that contributes to host defense against mycobacteria in infected macrophages.

Indexed as

Flow CytometryFluorescent Antibody TechniqueGene Expression ProfilingHumansLeprosyMacrophagesMycobacterium InfectionsMycobacterium lepraeMycobacterium tuberculosisReal-Time Polymerase Chain ReactionS100A12 ProteinTranscriptomeS100A12 ProteinS100A12 protein, human

Identifiers

PMID27355424
PMCPMC4927120
OpenAlexW2470134329

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.