Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism

Catherine Werts; Richard I. Tapping; John C. Mathison; Tsung Hsien Chuang; Vladimir Kravchenko; Isabelle Saint Girons; David A. Haake; Paul J. Godowski; Fumitaka Hayashi; Adrian Ozinsky; David M. Underhill; Carsten J. Kirschning; Hermann Wagner; Alan Aderem; Peter S. Tobias; Richard J. Ulevitch

doi:10.1038/86354

Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism

Catherine Werts, Richard I. Tapping, John C. Mathison, Tsung Hsien Chuang, Vladimir Kravchenko, Isabelle Saint Girons, David A. Haake, Paul J. Godowski, Fumitaka Hayashi, Adrian Ozinsky, David M. Underhill, Carsten J. Kirschning, Hermann Wagner, Alan Aderem, Peter S. Tobias, Richard J. Ulevitch

Research output: Contribution to journal › Article › peer-review

Abstract

Leptospira interrogans are zoonotic pathogens that have been linked to a recent increased incidence of morbidity and mortality in highly populated tropical urban centers. They are unique among invasive spirochetes in that they contain outer membrane lipopolysaccharide (LPS) as well as lipoproteins. Here we show that both these leptospiral outer membrane constituents activate macrophages through CD14 and the Toll-like receptor 2 (TLR2). Conversely, it seems that TLR4, a central component for recognition of Gram-negative LPS, is not involved in cellular responses to L. interrogans. We also show that for intact L. interrogans, it is LPS, not lipoprotein, that constitutes the predominant signaling component for macrophages through a TLR2 pathway. These data provide a basis for understanding the innate immune response caused by leptospirosis and demonstrate a new ligand specificity for TLR2.

Original language	English (US)
Pages (from-to)	346-352
Number of pages	7
Journal	Nature Immunology
Volume	2
Issue number	4
DOIs	https://doi.org/10.1038/86354
State	Published - Apr 2001
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/86354

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Werts, C., Tapping, R. I., Mathison, J. C., Chuang, T. H., Kravchenko, V., Saint Girons, I., Haake, D. A., Godowski, P. J., Hayashi, F., Ozinsky, A., Underhill, D. M., Kirschning, C. J., Wagner, H., Aderem, A., Tobias, P. S., & Ulevitch, R. J. (2001). Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nature Immunology, 2(4), 346-352. https://doi.org/10.1038/86354

Werts, C, Tapping, RI, Mathison, JC, Chuang, TH, Kravchenko, V, Saint Girons, I, Haake, DA, Godowski, PJ, Hayashi, F, Ozinsky, A, Underhill, DM, Kirschning, CJ, Wagner, H, Aderem, A, Tobias, PS & Ulevitch, RJ 2001, 'Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism', Nature Immunology, vol. 2, no. 4, pp. 346-352. https://doi.org/10.1038/86354

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title = "Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism",

abstract = "Leptospira interrogans are zoonotic pathogens that have been linked to a recent increased incidence of morbidity and mortality in highly populated tropical urban centers. They are unique among invasive spirochetes in that they contain outer membrane lipopolysaccharide (LPS) as well as lipoproteins. Here we show that both these leptospiral outer membrane constituents activate macrophages through CD14 and the Toll-like receptor 2 (TLR2). Conversely, it seems that TLR4, a central component for recognition of Gram-negative LPS, is not involved in cellular responses to L. interrogans. We also show that for intact L. interrogans, it is LPS, not lipoprotein, that constitutes the predominant signaling component for macrophages through a TLR2 pathway. These data provide a basis for understanding the innate immune response caused by leptospirosis and demonstrate a new ligand specificity for TLR2.",

author = "Catherine Werts and Tapping, {Richard I.} and Mathison, {John C.} and Chuang, {Tsung Hsien} and Vladimir Kravchenko and {Saint Girons}, Isabelle and Haake, {David A.} and Godowski, {Paul J.} and Fumitaka Hayashi and Adrian Ozinsky and Underhill, {David M.} and Kirschning, {Carsten J.} and Hermann Wagner and Alan Aderem and Tobias, {Peter S.} and Ulevitch, {Richard J.}",

note = "Funding Information: Supported by grants AI-15136, GM-28485 and GM-37696 from the National Institutes of Health (to R. J. U.), a Beginning Grant-in-Aid from the American Heart Association Western States Affiliate (to R. I.T.) and by a postdoctoral fellowship from North Atlantic Treaty Organization (to C.W.).",

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doi = "10.1038/86354",

language = "English (US)",

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pages = "346--352",

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AU - Werts, Catherine

AU - Tapping, Richard I.

AU - Mathison, John C.

AU - Chuang, Tsung Hsien

AU - Kravchenko, Vladimir

AU - Saint Girons, Isabelle

AU - Haake, David A.

AU - Godowski, Paul J.

AU - Hayashi, Fumitaka

AU - Ozinsky, Adrian

AU - Underhill, David M.

AU - Kirschning, Carsten J.

AU - Wagner, Hermann

AU - Aderem, Alan

AU - Tobias, Peter S.

AU - Ulevitch, Richard J.

N1 - Funding Information: Supported by grants AI-15136, GM-28485 and GM-37696 from the National Institutes of Health (to R. J. U.), a Beginning Grant-in-Aid from the American Heart Association Western States Affiliate (to R. I.T.) and by a postdoctoral fellowship from North Atlantic Treaty Organization (to C.W.).

PY - 2001/4

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N2 - Leptospira interrogans are zoonotic pathogens that have been linked to a recent increased incidence of morbidity and mortality in highly populated tropical urban centers. They are unique among invasive spirochetes in that they contain outer membrane lipopolysaccharide (LPS) as well as lipoproteins. Here we show that both these leptospiral outer membrane constituents activate macrophages through CD14 and the Toll-like receptor 2 (TLR2). Conversely, it seems that TLR4, a central component for recognition of Gram-negative LPS, is not involved in cellular responses to L. interrogans. We also show that for intact L. interrogans, it is LPS, not lipoprotein, that constitutes the predominant signaling component for macrophages through a TLR2 pathway. These data provide a basis for understanding the innate immune response caused by leptospirosis and demonstrate a new ligand specificity for TLR2.

AB - Leptospira interrogans are zoonotic pathogens that have been linked to a recent increased incidence of morbidity and mortality in highly populated tropical urban centers. They are unique among invasive spirochetes in that they contain outer membrane lipopolysaccharide (LPS) as well as lipoproteins. Here we show that both these leptospiral outer membrane constituents activate macrophages through CD14 and the Toll-like receptor 2 (TLR2). Conversely, it seems that TLR4, a central component for recognition of Gram-negative LPS, is not involved in cellular responses to L. interrogans. We also show that for intact L. interrogans, it is LPS, not lipoprotein, that constitutes the predominant signaling component for macrophages through a TLR2 pathway. These data provide a basis for understanding the innate immune response caused by leptospirosis and demonstrate a new ligand specificity for TLR2.

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Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism

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