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

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 gener...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2016-06, Vol.12 (6), p.e1005705-e1005705
Main Authors: Realegeno, Susan, Kelly-Scumpia, Kindra M, Dang, Angeline Tilly, Lu, Jing, Teles, Rosane, Liu, Philip T, Schenk, Mirjam, Lee, Ernest Y, Schmidt, Nathan W, Wong, Gerard C L, Sarno, Euzenir N, Rea, Thomas H, Ochoa, Maria T, Pellegrini, Matteo, Modlin, Robert L
Format: Article
Language:English
Subjects:
Analysis
Antimicrobial agents
Antimicrobial peptides
Biology and Life Sciences
Defense mechanisms
Flow Cytometry
Fluorescent Antibody Technique
Funding
Gene expression
Gene Expression Profiling
Genomics
Health aspects
Humans
Immune system
Infections
Infectious diseases
Laboratories
Leprosy
Leprosy - immunology
Macrophages
Macrophages - immunology
Macrophages - microbiology
Medicine and Health Sciences
Mycobacteria
Mycobacterium Infections - immunology
Mycobacterium leprae
Mycobacterium leprae - immunology
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Real-Time Polymerase Chain Reaction
RNA sequencing
Rodents
S100A12 Protein - immunology
Spectrum analysis
Transcriptome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1005705