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Leptospirosis: A Toll Road from B Lymphocytes

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Author(s): Catherine Werts

Journal: Chang Gung Medical Journal
ISSN 2072-0939

Volume: 33;
Issue: 06;
Start page: 591;
Date: 2010;
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Keywords: leptospirosis | Toll-like receptors | TLR-deficient mice

ABSTRACT
Leptospirosis is a widespread zoonosis caused byLeptospira interrogans, a pathogen transmitted by asymptomaticinfected rodents. Leptospiral lipoproteins andlipopolysaccharide (LPS) have been shown to stimulate murinecells via Toll-like receptors (TLRs) 2 and 4. Host defensemechanisms remain obscure, although TLR4 has been associatedwith clearing Leptospira. In a recent study, we showedthat in response to Leptospira infection, double (TLR2 andTLR4) knock-out (DKO) mice unexpectedly developed TLRindependentpro-inflammatory responses, and rapidly diedfrom severe hepatic and renal failure. Subsequent analysis ofchimeric and transgenic mice identified B-cells as the cruciallymphocyte subset responsible for the clearance of Leptospira,initially through the production of specific TLR4-dependentimmunoglobulin M (IgM), directed against the LPS ofLeptospira, and subsequently through specific IgG production, which is impaired in DKOmice. We also identified the protective, tissue-compartmentalized, TLR2/TLR4-mediatedproduction of interferon-γ (IFN-γ) by B- and T-lymphocytes. Overall, our recent findingsdemonstrate that TLR2 and TLR4 both play a key role in the early control of leptospirosis,and constitute the first line of defense against Leptospira, confirming previous in vitro datashowing that both LPS and lipoprotein play a crucial role in cell activation. However, if thisfirst line of defense is by-passed, Leptospira can induce a deleterious inflammation in thetarget organs, and this does not rely on TLR activation.
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