| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Institut National de la Santé et de la Recherche Médicale U773, Centre de Recherche Biomédicale Bichat-Beaujon (CRB3), Paris France; Université Paris 7, Denis Diderot, Paris, France;
Service d’Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire de Poitiers, Poitiers, France;
Unité de Réponses Précoces aux Parasites et Immunopathologie, Institut National de la Recherche Agronomique, Paris, France; and
Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, Paris, France
TLR4 plays a central role in resistance to pyelonephritis caused by uropathogenic Escherichia coli (UPEC). It has been suggested that renal tubule epithelial cells expressing TLRs may play a key role in inflammatory disorders and in initiating host defenses. In this study we used an experimental mouse model of ascending urinary tract infection to show that UPEC isolates preferentially adhered to the apical surface of medullary collecting duct (MCD) intercalated cells. UPEC-infected C3H/HeJ (Lpsd) mice carrying an inactivating mutation of tlr4 failed to clear renal bacteria and exhibited a dramatic slump in proinflammatory mediators as compared with infected wild-type C3H/HeOuJ (Lpsn) mice. However, the level of expression of the leukocyte chemoattractants MIP-2 and TNF-
still remained greater in UPEC-infected than in naive C3H/HeJ (Lpsd) mice. Using primary cultures of microdissected Lpsn MCDs that expressed TLR4 and its accessory molecules MD2, MyD88, and CD14, we also show that UPECs stimulated both a TLR4-mediated, MyD88-dependent, TIR domain-containing adaptor-inducing IFN-
-independent pathway and a TLR4-independent pathway, leading to bipolarized secretion of MIP-2. Stimulation by UPECs of the TLR4-mediated pathway in Lpsn MCDs leads to the activation of NF-
B, and MAPK p38, ERK1/2, and JNK. In addition, UPECs stimulated TLR4-independent signaling by activating a TNF receptor-associated factor 2-apoptosis signal-regulatory kinase 1-JNK pathway. These findings demonstrate that epithelial collecting duct cells are actively involved in the initiation of an immune response via several distinct signaling pathways and suggest that intercalated cells play an active role in the recognition of UPECs colonizing the kidneys.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was funded by Institut National de la Santé et de la Recherche Médicale (INSERM) and by Institut Pasteur Grant PTR 165 (to C.L.B. and D.B.-G.). A.V. was in receipt of an Interface INSERM-AP-HP fellowship.
2 C.L.B, D.B.-G, and A.V. made equal contributions to this work.
3 Address correspondence and reprint requests to Dr. Alain Vandewalle, Institut National de la Santé et de la Recherche Médicale U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Unité de Formation et de Recherche de Médecine Xavier Bichat, BP 416, 16 Rue Henri Huchard, F-75870 Paris Cedex 18, France. E-mail address: vandewal{at}bichat.inserm.fr
4 Abbreviations used in this paper: UTI, urinary tract infection; AQP-2, aquaporin-2; ASK1, apoptosis signal-regulatory kinase 1; CFTR, cystic fibrosis transmembrane conductance regulator; ClC-5, chloride channel 5; ENaC, epithelial sodium channel; iNOS, inducible NO synthase; MAPKAPK-2, MAPK-activated protein kinase 2; MCD, medullary collecting duct; ROS, reactive oxygen species; TRAF, TNF receptor-associated factor; TRIF, TIR domain-containing adaptor inducing IFN-; UPEC, uropathogenic Escherichia coli.
This article has been cited by other articles:
|
|
 |
|
  S. B. Mkaddem, C. Werts, J.-M. Goujon, M. Bens, E. Pedruzzi, E. Ogier-Denis, and A. Vandewalle Heat Shock Protein gp96 Interacts with Protein Phosphatase 5 and Controls Toll-like Receptor 2 (TLR2)-mediated Activation of Extracellular Signal-regulated Kinase (ERK) 1/2 in Post-hypoxic Kidney Cells J. Biol. Chem., May 1, 2009; 284(18): 12541 - 12549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Martinez-Jehanne, L. du Merle, C. Bernier-Febreau, C. Usein, A. Gassama-Sow, A.-A. Wane, M. Gouali, M. Damian, A. Aidara-Kane, Y. Germani, et al. Role of Deoxyribose Catabolism in Colonization of the Murine Intestine by Pathogenic Escherichia coli Strains Infect. Immun., April 1, 2009; 77(4): 1442 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Chassin, S. Vimont, F. Cluzeaud, M. Bens, J.-M. Goujon, B. Fernandez, A. Hertig, E. Rondeau, G. Arlet, M. W. Hornef, et al. TLR4 Facilitates Translocation of Bacteria across Renal Collecting Duct Cells J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2364 - 2374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. C. Smith, S. B. Rasmussen, K. K. Grande, R. M. Conran, and A. D. O'Brien Hemolysin of Uropathogenic Escherichia coli Evokes Extensive Shedding of the Uroepithelium and Hemorrhage in Bladder Tissue within the First 24 Hours after Intraurethral Inoculation of Mice Infect. Immun., July 1, 2008; 76(7): 2978 - 2990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Banas, B. Banas, K. L. Hudkins, T. A. Wietecha, M. Iyoda, E. Bock, P. Hauser, J. W. Pippin, S. J. Shankland, K. D. Smith, et al. TLR4 Links Podocytes with the Innate Immune System to Mediate Glomerular Injury J. Am. Soc. Nephrol., April 1, 2008; 19(4): 704 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Chassin, M. W. Hornef, M. Bens, M. Lotz, J.-M. Goujon, S. Vimont, G. Arlet, A. Hertig, E. Rondeau, and A. Vandewalle Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin J. Exp. Med., November 26, 2007; 204(12): 2837 - 2852. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
