New study showing how LPS triggers immune response

[Effi]

http://www.jbc.org/content/early/2016/06/29/jbc.M116.741256
Dectin-2 recognises mannosylated O-antigens of human opportunistic pathogens and augments lipopolysaccharide activation of myeloid cells

1. Alexandra Wittmann1,
2. Dimitra Lamprinaki1,
3. Kristian M. Bowles2,
4. Ewa Katzenellenbogen3,
5. Yuriy A. Knirel4,
6. Chris Whitfield5,
7. Takashi Nishimura6,
8. Naoki Matsumoto6,
9. Kazuo Yamamoto6,
10. Yoichiro Iwakura7,
11. Shinobu Saijo8 and
12. Norihito Kawasaki1*

First Published on June 29, 2016
doi: 10.1074/jbc.M116.741256jbc.M116.741256.

Lipopolysaccharide (LPS) consists of a relatively conserved region of lipid A and core-oligosaccharide, and a highly variable region of O-antigen polysaccharide. While lipid A is known to bind to the toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex, the role of the O-antigen remains unclear.

Here we report a novel molecular interaction between dendritic cell-associated C-type lectin-2 (Dectin-2) and the mannosylated O-antigen found in a human opportunistic pathogen Hafnia alvei PCM 1223, which has a repeating unit of [-Man-α1,3-Man-α1,2-Man-α1,2-Man-α1,2-Man-α1,3-]. H. alvei LPS induced higher levels of TNFα and IL-10 from mouse bone marrow-derived dendritic cells (BM-DCs), when compared to Salmonella enterica O66 LPS which has a repeat of [-Gal-α1,6-Gal-α1,4-[Glc-β1,3]GalNAc-α1,3-GalNAc-β1,3-].

In a cell-based reporter assay, Dectin-2 was shown to recognise H. alvei LPS. This binding was inhibited by mannosidase treatment of H. alvei LPS and by mutations in the carbohydrate-binding domain of Dectin-2, demonstrating that H. alvei LPS is a novel glycan ligand of Dectin-2. The enhanced cytokine production by H. alvei LPS was Dectin-2 dependent, as Dectin-2 knockout BM-DCs failed to do so. This receptor crosstalk between Dectin-2 and TLR4 involved events including spleen tyrosine kinase (Syk) activation and receptor juxtaposition.

Furthermore, another mannosylated LPS from Escherichia coli O9a, also bound to Dectin-2 and augmented TLR4 activation of BM-DCs. Taken together, these data indicate that mannosylated O-antigens from several gram-negative bacteria augment TLR4 responses through interaction with Dectin-2.

Article on the paper: http://www.ifr.ac.uk/news/latest-news/2016/07/new-insights-how-we-fight-bacterial-infection/

A new study has found a novel way in which certain bacteria are recognised and trigger our immune system.

Dr Norihito Kawasaki from the Institute of Food Research has led a group of researchers investigating the role of molecules called lipopolysaccharides. These molecules are found on the outer surface of a large group of bacteria, where they play a key role in protecting the bacteria. But they also give away their identity to molecules that play a role in our immune defence.

Now, in a paper published in the Journal of Biological Chemistry, the researchers have uncovered new details about how this recognition happens, and how this information is relayed to the immune system so that it can coordinate a response.

Lipopolysaccharides, as their name suggests are made up of a fatty lipid section attached to a sugary polysaccharide part. Whilst the lipid part is relatively similar between different bacteria, the polysaccharide is highly variable. Lipopolysaccharides (LPS) have been recognised for their role in triggering immune response, but this new research adds to our understanding of how this happens and helps explain how we react to infection by certain bacteria.

 

[Groggy Doggy]

"Whilst the lipid part is relatively similar between different bacteria, the polysaccharide is highly variable"

@Effi I like this research, a true international effort. It's very interesing and I hope future research will reveal what causes the variability.

 

[Justin30]

It would be be very beneficial for a standardized test to show the amount of LPS in blood serum.

This being said CD14 is a marker for LPS but is not readily used.

Further drugs that are safer in the reduction of LPS in serum need to be developed to tackle this problem as LPS seems to interefere with many biological process such as the breakdown of vitamins, minerals and amino acids.