Published ahead of print on September 24, 2004, doi:10.1164/rccm.200404-525OC
Am. J. Respir. Crit. Care Med., Volume 170, Number 12, December 2004, 1367-1374
A more recent version of this article appeared on December 15, 2004
Submitted on April 21, 2004
Accepted on September 17, 2004
Non-mannose-capped Lipoarabinomannan Induces Lung Inflammation via Toll-like Receptor 2
Catharina W Wieland1*, Sylvia Knapp1, Sandrine Florquin2, Alex F de Vos1, Kiyoshi Takeda3, Shizuo Akira3, Douglas T Golenbock4, Annelies Verbon5, and Tom van der Poll5
1 Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands,
2 Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands,
3 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan,
4 Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA,
5 Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and Aids, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: c.wieland{at}amc.uva.nl.
Non-mannose-capped lipoarabinomannan (AraLAM) is part of the cell membrane of atypical mycobacteria. To determine the capacity of AraLAM to induce lung inflammation in vivo , and to determine the signalling receptors involved herein, wild-type (WT) mice, Lipopolysaccharide Binding Protein knock-out (LBP KO) mice, CD14 deficient (CD14 KO) mice, Toll-like receptor (TLR) 4 mutant mice or TLR2 KO mice were intranasally inoculated with purified AraLAM. AraLAM induced high lung levels of Tumor Necrosis Factor (TNF), Interleukin (IL-)1 , IL-6 and KC and an influx of neutrophils into the pulmonary compartment of WT mice. LBP KO, CD14 KO and TLR4 mutant mice displayed similar inflammatory responses as WT mice, whereas in TLR2 KO mice AraLAM-induced lung inflammation was strongly diminished. In addition, TLR2 KO mice, but not CD14 KO or TLR4 mutant mice, displayed a delayed clearance of pulmonary infection with the atypical AraLAM expressing Mycobacterium (M.) smegmatis. These data indicate that TLR2 is the signaling receptor for purified AraLAM in the lung in vivo and that this receptor contributes to an effective clearance of M. smegmatis from the pulmonary compartment.
Key words: pulmonary, bacterial antigens, knock-out, mycobacterium
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