Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor-2

Becker, Ingeborg; Salaiza, Norma; Aguirre, Maria Teresa Holguín; Delgado, João; Carrillo-Carrasco, Nuria; Kobeh, Laila Gutiérrez; Ruíz, Adi Estela Lazos; Cervantes, Rocely; Torres, Armando Pérez; Cabrera, Nallely; González, Augusto Silva; Maldonado, Carmen; Isibasí, Armando

doi:10.1016/s0166-6851(03)00160-9

Cited by 316 publications

(321 citation statements)

References 51 publications

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“…The cytokines promotes an up-regulation of the TLR2 to maintain a continuous inflammatory response by unknown mechanism 9 . Our results are similar to those obtained in experimental models of L. major in mice 4,6,8 . Lipophosphoglycan, a polymer of repeating Galβ1-4Manα-PO 4 units and a prominent Leishmania surface glycoconjugate 14 , activates both mouse macrophages and human NK cells through TLR2 4,6 .…”

Section: Discussionsupporting

confidence: 91%

“…Our results are similar to those obtained in experimental models of L. major in mice 4,6,8 . Lipophosphoglycan, a polymer of repeating Galβ1-4Manα-PO 4 units and a prominent Leishmania surface glycoconjugate 14 , activates both mouse macrophages and human NK cells through TLR2 4,6 . The binding of lipophosphoglycan to TLR2 enhances IFN-γ and TNF-α production and nuclear translocation of NF-κB 18 .…”

Section: Discussionsupporting

confidence: 91%

“…Recent studies revealed that TLR2 and TLR4 contribute to the recognition of Leishmania major and to the subsequent immune response 4,8,15 . Nevertheless, discrepancy in TLR signaling has been observed when in vitro and in vivo studies have been published 2,[10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

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Expression of TLR2 and TLR4 in lesions of patients with tegumentary american leishmaniasis

Tuon

Fernandes

Duarte

et al. 2012

Rev. Inst. Med. trop. S. Paulo

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SUMMARYObjectives: The aim of this study was to describe the pattern of expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in skin biopsies of patients with American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis. Methods: This prospective study evaluated 12 patients with ATL caused by Leishmania braziliensis confirmed by polymerase chain reaction. Immunohistochemistry was performed to determine the expression of TLR2 and TLR4. The number of NK cells, dendritic cells and macrophages in the tissue were calculated. The cytokine expression was determined using the anti-TNF-α, anti-IFN-γ, anti-IL-1 and anti-IL-6. Double immunostaining reactions were used to determine the cell expressing TLR2 and TLR4. Results: The numbers of cells expressing TLR2 and TLR4 were 145.48 ± 82.46 cell/mm 2 and 3.26 ± 4.11 cell/mm 2 respectively (p < 0.05). There was no correlation of TLR2 and TLR4 with the amount of cytokines and the number of NK cells, dendritic cells or macrophages. The double immunostaining revealed that TLR2 was expressed by macrophages. Conclusion: In human cutaneous leishmaniasis caused by Leishmania braziliensis, TLR2 is the most common TLR expressed during active disease, mainly by macrophages although without correlation with the amount of cytokines and number of cells.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

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Expression of TLR2 and TLR4 in lesions of patients with tegumentary american leishmaniasis

Tuon

Fernandes

Duarte

et al. 2012

Rev. Inst. Med. trop. S. Paulo

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“…Mice infected with Salmonella begin to produce IFN-␥ ϳ3-5 days after the onset of infection (32), and TLR4-deficient mice retain the ability to produce IFN-␥ in response to Salmonella (33). Sources of IFN-␥ include NK cells (34), which can be activated by stimulation of receptors such as TLR2 (35). Although the production of IFN-␥ can eventually overcome the absence of LPS-TLR4 signaling for the stimulation of iNOS expression, the delayed synthesis of NO is likely to be detrimental to the infected host.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4 Dependence of Innate and Adaptive Immunity to Salmonella: Importance of the Kupffer Cell Network

Vázquez‐Torres

Vallance

Bergman

et al. 2004

The Journal of Immunology

158

103

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Mammalian cells recognize LPS from Gram-negative bacteria via the Toll-like receptor 4 (TLR4) complex. During experimental Salmonella infection, C3H/HeJ mice carrying a dominant-negative mutation in TLR4 exhibited delayed chemokine production, impaired NO generation, and attenuated cellular immune responses. However, dramatically enhanced bacterial growth within the Kupffer cell network before the recruitment of inflammatory cells appeared to be primarily responsible for the early demise of Salmonella-infected TLR4-deficient mice. LPS-TLR4 signaling plays an essential role in the generation of both innate and adaptive immune responses throughout the course of infection with Gram-negative bacteria. Alternative pattern-recognition receptors cannot completely compensate for the loss of TLR4, and compensation occurs at the expense of an increased microbial burden.

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“…L. major, LPG, a phosphoglycan belonging to a family of unique Leishmania glycol-conjugates, up regulates both mRNA and the membrane expression of TLR-2 in NK cells. Additionally, IFN c and TNF a production and nuclear translocation of NFkB are enhanced (Becker et al 2003). LPG also blocks the production of NO and oxidative burst by binding to the regulatory domain of PKC (Shadab and Ali 2011).…”

Section: Introductionmentioning

confidence: 99%

Signaling networks in Leishmania macrophages deciphered through integrated systems biology: a mathematical modeling approach

2013

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Network of signaling proteins and functional interaction between the infected cell and the leishmanial parasite, though are not well understood, may be deciphered computationally by reconstructing the immune signaling network. As we all know signaling pathways are well-known abstractions that explain the mechanisms whereby cells respond to signals, collections of pathways form networks, and interactions between pathways in a network, known as cross-talk, enables further complex signaling behaviours. In silico perturbations can help identify sensitive crosstalk points in the network which can be pharmacologically tested. In this study, we have developed a model for immune signaling cascade in leishmaniasis and based upon the interaction analysis obtained through simulation, we have developed a model network, between four signaling pathways i.e., CD14, epidermal growth factor (EGF), tumor necrotic factor (TNF) and PI3 K mediated signaling. Principal component analysis of the signaling network showed that EGF and TNF pathways can be potent pharmacological targets to curb leishmaniasis. The approach is illustrated with a proposed workable model of epidermal growth factor receptor (EGFR) that modulates the immune response. EGFR signaling represents a critical junction between inflammation related signal and potent cell regulation machinery that modulates the expression of cytokines.

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Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor-2

Cited by 316 publications

References 51 publications

Expression of TLR2 and TLR4 in lesions of patients with tegumentary american leishmaniasis

Expression of TLR2 and TLR4 in lesions of patients with tegumentary american leishmaniasis

Toll-Like Receptor 4 Dependence of Innate and Adaptive Immunity to Salmonella: Importance of the Kupffer Cell Network

Signaling networks in Leishmania macrophages deciphered through integrated systems biology: a mathematical modeling approach

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