Abstract |
Two different Toll-like receptors (TLRs) have been shown to play a role in host responses to Leishmania infection. TLR-2 is involved in parasite survival in macrophages upon activation by lipophosphoglycan (LPG), a virulence factor expressed by Leishmania. In contrast, activation of TLR-9 has been shown to promote a host-protective response. However, whether there is a relationship between the interaction of LPG and TLR-2, on one hand, with the effect of TLR-9, on the other hand, remains unknown. In this study, we report that in-vitro infection of macrophages with a L. major parasite with high expression levels of LPG results in decreased TLR-9 expression compared to infection with a L. major parasite with lower expression levels of LPG. Addition of anti-LPG as well as anti-TLR-2 antibodies prevents this reduction of TLR-9 expression. Also, the addition of purified LPG to macrophages results in a decrease of TLR-9 expression, which is shown to be mediated by transforming growth factor (TGF)-β and interleukin (IL)-10. Finally, in-vitro treatment of macrophages with anti-LPG and/or anti-TLR-2 antibodies before infection reduces the number of amastigotes in macrophages and co-treatment of mice with anti-TLR-2 antibodies and cytosine- phosphate- guanosine (CpG) reduces footpad swelling and parasite load in the draining lymph nodes, accompanied by an interferon (IFN)-γ-predominant T cell response. Thus, for the first time, we show how interactions between LPG and TLR-2 reduce anti-leishmanial responses via cytokine-mediated decrease of TLR-9 expression.
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Authors | S Srivastava, S P Pandey, M K Jha, H S Chandel, B Saha |
Journal | Clinical and experimental immunology
(Clin Exp Immunol)
Vol. 172
Issue 3
Pg. 403-9
(Jun 2013)
ISSN: 1365-2249 [Electronic] England |
PMID | 23600828
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2013 British Society for Immunology. |
Chemical References |
- Glycosphingolipids
- IL10 protein, mouse
- Tlr2 protein, mouse
- Tlr9 protein, mouse
- Toll-Like Receptor 2
- Toll-Like Receptor 9
- Transforming Growth Factor beta
- lipophosphonoglycan
- Interleukin-10
- Nitric Oxide Synthase Type II
- Nos2 protein, mouse
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Topics |
- Animals
- CpG Islands
(immunology)
- Gene Expression
- Glycosphingolipids
(genetics, immunology)
- Host-Parasite Interactions
(genetics, immunology)
- Immune Tolerance
- Interleukin-10
(genetics, metabolism)
- Leishmania major
(genetics, immunology, pathogenicity)
- Leishmaniasis, Cutaneous
(genetics, immunology, parasitology, therapy)
- Macrophage Activation
- Macrophages
(immunology, parasitology)
- Mice
- Mice, Inbred BALB C
- Nitric Oxide Synthase Type II
(genetics, metabolism)
- Toll-Like Receptor 2
(antagonists & inhibitors, genetics, metabolism)
- Toll-Like Receptor 9
(genetics, metabolism)
- Transforming Growth Factor beta
(genetics, metabolism)
- Virulence
(immunology)
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