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The Nod1 stimulating agonists C12-iEDAP and FK156 stimulate neutrophil bacterial phagocytosis impaired by CsA and increase renal defenses against UPEC.

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posted on 2013-01-31, 02:31 authored by Emilie Tourneur, Sanae Ben Mkaddem, Cécilia Chassin, Marcelle Bens, Jean-Michel Goujon, Nicolas Charles, Christophe Pellefigues, Meryem Aloulou, Alexandre Hertig, Renato C. Monteiro, Stephen E. Girardin, Dana J. Philpott, Eric Rondeau, Carole Elbim, Catherine Werts, Alain Vandewalle

(A) Illustrations and quantification of Texas red-coupled E. coli internalized by circulating neutrophils collected from WT mice treated with CsA for 5 days then with CsA plus C12-iEDAP (80 µg per mouse) for a further 5 h. Neutrophils were isolated from the blood of 3 mice under each of the conditions tested. Representative values (mean ± SE) of the mean counts (9–15 per condition) from 3 independent experiments. Cell membranes were stained with WGA Alexa Fluor 647 conjugate. Bars, 10 µm. (B and C) Bacterial counts (B) and MPO activity (C) in kidneys of CsA-treated WT mice pre-treated or not with C12-iEDAP (n = 6), FK156 (n = 9), or MDP (n = 7) (80 µg per mouse), and then challenged 24 h later with E. coli HT7. (D) Immunoblot analysis of Nod1 and the corresponding ß-actin in the post-infected kidney homogenates from vehicle- and CsA-treated mice which had received FK156 12 h before UPEC inoculation. (E) Production of CXCL2 and CXCL1 in the 24 h post-infected kidneys from vehicle- or CsA-treated WT mice pre-treated or not with C12-iEDAP or FK156 (n = 6–9 per group). *, p<0.05 (A, C, E, Two-tailed, unpaired Student's t test; B, Mann-Whitney test).