NOD2 triggers an interleukin-32-dependent human dendritic cell program in leprosy

David Geffen School of Medicine at University of California–Los Angeles (UCLA). Department of Medicine. Division of Dermatology. Los Angeles, CA, USA.
David Geffen School of Medicine at University of California–Los Angeles (UCLA). Department of Medicine. Division of Dermatology. Los Angeles, CA, USA.
David Geffen School of Medicine at University of California–Los Angeles (UCLA). Department of Medicine. Division of Dermatology. Los Angeles, CA, USA.
David Geffen School of Medicine at University of California–Los Angeles (UCLA). Department of Medicine. Division of Dermatology. Los Angeles, CA, USA .
David Geffen School of Medicine at University of California–Los Angeles (UCLA). Department of Medicine. Division of Dermatology. Los Angeles, CA, USA.
David Geffen School of Medicine at University of California–Los Angeles (UCLA). Department of Medicine. Division of Dermatology. Los Angeles, CA, USA.
Crump Institute for Molecular Imaging. Department of Molecular and Medical Pharmacology. Institute for Molecular Medicine. Jonsson Comprehensive Cancer Center and California NanoSystems Institute. David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.
University of Southern California School of Medicine. Department of Dermatology,. Los Angeles, CA, USA.
Crump Institute for Molecular Imaging. Department of Molecular and Medical Pharmacology. Institute for Molecular Medicine. Jonsson Comprehensive Cancer Center and California NanoSystems Institute. David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Konkuk University. Department of Biomedical Science and Technology. Seoul, Korea.
David Geffen School of Medicine at UCLA. Department of Microbiology, Immunology and Molecular Genetics. Los Angeles, CA, USA.
David Geffen School of Medicine at University of California–Los Angeles (UCLA). Department of Medicine. Division of Dermatology. Los Angeles, CA, USA / David Geffen School of Medicine at UCLA. Department of Microbiology, Immunology and Molecular Genetics. Los Angeles, CA, USA..

Abstract

It is unclear whether the ability of the innate immune system to recognize distinct ligands from a single microbial pathogen via multiple pattern recognition receptors (PRRs) triggers common pathways or differentially triggers specific host responses. In the human mycobacterial infection leprosy, we found that activation of monocytes via nucleotide-binding oligomerization domain-containing protein 2 (NOD2) by its ligand muramyl dipeptide, as compared to activation via heterodimeric Toll-like receptor 2 and Toll-like receptor 1 (TLR2/1) by triacylated lipopeptide, preferentially induced differentiation into dendritic cells (DCs), which was dependent on a previously unknown interleukin-32 (IL-32)-dependent mechanism. Notably, IL-32 was sufficient to induce monocytes to rapidly differentiate into DCs, which were more efficient than granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived DCs in presenting antigen to major histocompatibility complex (MHC) class I-restricted CD8(+) T cells. Expression of NOD2 and IL-32 and the frequency of CD1b(+) DCs at the site of leprosy infection correlated with the clinical presentation; they were greater in patients with limited as compared to progressive disease. The addition of recombinant IL-32 restored NOD2-induced DC differentiation in patients with the progressive form of leprosy. In conclusion, the NOD2 ligand-induced, IL-32-dependent DC differentiation pathway contributes a key and specific mechanism for host defense against microbial infection in humans.

Keywords in Portuguese

Hanseníase
Interleucina-32
Células dendríticas
Proteína Adaptadora de Sinalização NOD2

Keywords

NOD2
Leprosy
human dendritic cell
interleukin-32

Publisher

Nature Publishing Group

Citation

SCHENK, Mirjam; et al. NOD2 triggers an interleukin-32–dependent human dendritic cell program in leprosy. Nat Med., v.18, n.4, p.555–563, 2012.

DOI

10.1038/nm.2650

ISSN

1078-8956

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/16781

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Restricted access

Embargo date

2030-01-01

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