The lipooligosaccharide of the gut symbiont Akkermansia muciniphila exhibits a remarkable structure and TLR signaling capacity

The cell-envelope of Gram-negative bacteria contains endotoxic lipopolysaccharides (LPS) that are recognized by the innate immune system via Toll-Like Receptors (TLRs). The intestinal mucosal symbiont Akkermansia muciniphila is known to confer beneficial effects on the host and has a Gram-negative architecture. Here we show that A. muciniphila LPS lacks the O-polysaccharide repeating unit, with the resulting lipooligosaccharide (LOS) having unprecedented structural and signaling properties. The LOS consists of a complex glycan chain bearing two distinct undeca- and hexadecasaccharide units each containing three 2-keto-3-deoxy-D-manno-octulosonic acid (Kdo) residues. The lipid A moiety appears as a mixture of differently phosphorylated and acylated species and carries either linear or branched acyl moieties. Peritoneal injection of the LOS in mice increased higher gene expression of liver TLR2 than TLR4 (100-fold) and induced high IL-10 gene expression. A. muciniphila LOS was found to signal both through TLR4 and TLR2, whereas lipid A only induced TLR2 in a human cell line. We propose that the unique structure of the A. muciniphila LOS allows interaction with TLR2, thus generating an anti-inflammatory response as to compensate for the canonical inflammatory signaling associated with LOS and TLR4, rationalizing its beneficial host interaction.

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Publication Details

Journal
Nature Communications
Published
2024-09-27
DOI
https://doi.org/10.1038/s41467-024-52683-x
Citations
48
Primary Topic
Parasitic Infections and Diagnostics
Type
article
Field-Weighted Citation Impact
24.75

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article

The lipooligosaccharide of the gut symbiont Akkermansia muciniphila exhibits a remarkable structure and TLR signaling capacity

Flaviana Di Lorenzo, Simone Nicolardi, Hanne L. P. Tytgat, Matthias Van Hul et al.
48 citations
Nature Communications
Parasitic Infections and Diagnostics
24.75
article

The lipooligosaccharide of the gut symbiont Akkermansia muciniphila exhibits a remarkable structure and TLR signaling capacity

Flaviana Di Lorenzo, Simone Nicolardi, Hanne L. P. Tytgat, Matthias Van Hul, Antonio Molinaro, Hubert Plovier, Willem M. de Vos, Patrice D. Cani, Marco Fragai, Alba Silipo, Janneke Elzinga, Pilar García-Vello, Cristina De Castro, Marta Tiemblo‐Martìn
article en
48 citations

Abstract

The cell-envelope of Gram-negative bacteria contains endotoxic lipopolysaccharides (LPS) that are recognized by the innate immune system via Toll-Like Receptors (TLRs). The intestinal mucosal symbiont Akkermansia muciniphila is known to confer beneficial effects on the host and has a Gram-negative architecture. Here we show that A. muciniphila LPS lacks the O-polysaccharide repeating unit, with the resulting lipooligosaccharide (LOS) having unprecedented structural and signaling properties. The LOS consists of a complex glycan chain bearing two distinct undeca- and hexadecasaccharide units each containing three 2-keto-3-deoxy-D-manno-octulosonic acid (Kdo) residues. The lipid A moiety appears as a mixture of differently phosphorylated and acylated species and carries either linear or branched acyl moieties. Peritoneal injection of the LOS in mice increased higher gene expression of liver TLR2 than TLR4 (100-fold) and induced high IL-10 gene expression. A. muciniphila LOS was found to signal both through TLR4 and TLR2, whereas lipid A only induced TLR2 in a human cell line. We propose that the unique structure of the A. muciniphila LOS allows interaction with TLR2, thus generating an anti-inflammatory response as to compensate for the canonical inflammatory signaling associated with LOS and TLR4, rationalizing its beneficial host interaction.

Nature CommunicationsVol. 15(1)
University of Helsinki (FI), Leiden University Medical Center (NL), Netherlands Metabolomics Centre (NL), Nestlé (Switzerland) (CH), Federico II University Hospital (IT), Walloon Excellence in Lifesciences and Biotechnology (BE), Interuniversity Consortium for Magnetic Resonance (IT), University of Naples Federico II (IT), Wageningen University & Research (NL), UCLouvain (BE), The University of Osaka (JP)
European Commission, Fonds De La Recherche Scientifique - FNRS, Ministero della Salute, Ministero dell’Istruzione, dell’Università e della Ricerca, Ministero degli Affari Esteri e della Cooperazione Internazionale, Walloon excellence in life sciences and biotechnology, Horizon 2020 Framework Programme, HORIZON EUROPE Framework Programme
Openalex Percentile: Top 0%
Parasitic Infections and Diagnostics
24.75
DOIOpen Access PDFOpenAlex
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