Open AccessMuramylpeptide shedding modulates cell sensing of Shigella flexneri
Author(s) -
Nigro Giulia,
Fazio Luigi Lembo,
Martino Maria Celeste,
Rossi Giacomo,
Tattoli Ivan,
Liparoti Valeria,
De Castro Cristina,
Molinaro Antonio,
Philpott Dana J.,
Bernardini Maria Lina
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.01075.x
Subject(s) - shigella flexneri , biology , nod1 , shigella , microbiology and biotechnology , innate immune system , pathogen , nod2 , intracellular parasite , peptidoglycan , bacteria , escherichia coli , immune system , intracellular , immunology , salmonella , genetics , gene
Summary Bacterial infections trigger the activation of innate immunity through the interaction of pathogen‐associated molecular patterns (PAMPs) with pattern recognition molecules (PRMs). The nucleotide‐binding oligomerization domain (Nod) proteins are intracellular PRMs that recognize muramylpeptides contained in peptidoglycan (PGN) of bacteria. It is still unclear how Nod1 physically interacts with PGN, a structure internal to the Gram‐negative bacterial envelope. To contribute to the understanding of this process, we demonstrate that, like Escherichia coli , Bordetella pertussis and Neisseria gonorrheae , the Gram‐negative pathogen Shigella spontaneously releases PGN fragments and that this process can be increased by inactivating either ampG or mppA , genes involved in PGN recycling. Both Shigella mutants, but especially the strain carrying the mppA deletion, trigger Nod1‐mediated NF‐κB activation to a greater extent than the wild‐type strain. Likewise, muramylpeptides spontaneously shed by Shigella are able per se to trigger a Nod1‐mediated response consistent with the relative amount. Finally, we found that qualitative changes in muramylpeptide shedding can alter in vivo host responses to Shigella infection. Our findings support the idea that muramylpeptides released by pathogens during infection could modulate the immune response through Nod proteins and thereby influence the outcome of disease.