NOD1 PARTICIPATES IN THE INNATE IMMUNE RESPONSE TO PSEUDOMONAS
AERUGINOSA
Leonardo H. Travassos1,2*, Leticia A. M Carneiro1,2*, Stephen E. Girardin3, Ivo G. Boneca4,
Ramon Lemos1, Marcelo T. Bozza1 Regina C. P. Domingues1, Anthony J. Coyle6, John
Bertin6, Dana J. Philpott5§ and Maria Cristina Plotkowski2
1
Instituto de Microbiologia - Universidade Federal do Rio de Janeiro, 2Faculdade de
Ciências Médicas – Universidade do Estado do Rio de Janeiro, Brazil, 3Unité de Pathogénie
Microbienne Moleculaire 4Unité de Pathogénie Bacteriénne des Muqueuses, 5Groupe
d’Immunité Innée et Signalisation – Institut Pasteur, Paris, France, 6Millenium
Pharmaceuticals, Cambridge, Massachusetts, USA
The mammalian innate immunne system recognizes pathogen-associated molecular patterns
(PAMPs) through pathogen recognition receptors (PRRs). Nod1 has been recently
described as a cytosolic receptor that detects specifically DAP-containing muropeptides
from Gram-negative bacteria peptidoglycan. In the present study we investigated the
potential role of Nod1 in the innate immune response against the opportunistic pathogen P.
aeruginosa. We demonstrate that Nod1 detects the P. aeruginosa peptidoglycan leading to
NF-κB activation and that this activity is diminished in epithelial cells expressing a
dominant-negative Nod1 construct or in mouse embryonic fibroblasts from Nod1-knockout mice infected with P. aeruginosa. Finally, we demonstrate that the cytokine secretion
kinetics and bacterial killing are altered in Nod1-deficient cells infected with P. aeruginosa
in early stages of infection.
*these autors share the autorship of this work