Human NOD2 Recognizes Structurally Unique Muramyl Dipeptides from Mycobacterium leprae.

Schenk, Mirjam; Mahapatra, Sebabrata; Le, Phuonganh; Kim, Hee Jin; Choi, Aaron W; Brennan, Patrick J; Belisle, John T; Modlin, Robert L (2016). Human NOD2 Recognizes Structurally Unique Muramyl Dipeptides from Mycobacterium leprae. Infection and immunity, 84(9), pp. 2429-2438. American Society for Microbiology 10.1128/IAI.00334-16

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The innate immune system recognizes microbial pathogens via pattern recognition receptors. One such receptor, NOD2, via recognition of muramyl dipeptide (MDP), triggers a distinct network of innate immune responses, including the production of interleukin-32 (IL-32), which leads to the differentiation of monocytes into dendritic cells (DC). NOD2 has been implicated in the pathogenesis of human leprosy, yet it is not clear whether Mycobacterium leprae, which has a distinct MDP structure, can activate this pathway. We investigated the effect of MDP structure on the innate immune response, finding that infection of monocytes with M. leprae induces IL-32 and DC differentiation in a NOD2-dependent manner. The presence of the proximal l-Ala instead of Gly in the common configuration of the peptide side chain of M. leprae did not affect recognition by NOD2 or cytokine production. Furthermore, amidation of the d-Glu residue did not alter NOD2 activation. These data provide experimental evidence that NOD2 recognizes naturally occurring structural variants of MDP.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Schenk, Mirjam

ISSN:

0019-9567

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

01 Feb 2017 13:24

Last Modified:

01 Feb 2017 13:24

Publisher DOI:

10.1128/IAI.00334-16

PubMed ID:

27297389

BORIS DOI:

10.7892/boris.94576

URI:

https://boris.unibe.ch/id/eprint/94576

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