Infection of C57BL/10ScCr and C57BL/10ScNCr mice with<i>Leishmania major</i>reveals a role for Toll-like receptor 4 in the control of parasite replication

Kropf, Pascale; Freudenberg, Nikolaus; Kalis, Christoph; Modolell, Manuel; Herath, Shan; Galanos, Chris; Freudenberg, Marina A.; Müller, Ingrid

doi:10.1189/jlb.1003484

Cited by 78 publications

(75 citation statements)

References 75 publications

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“…We recently described the specific contribution of TLR4 to the control of parasite growth in both innate and adaptive immune responses following L. major infection (23,24). In our studies, a comparison of infections in C57BL10/ScN mice (which carry a null mutation in TLR4) (35,36) with those in TLR4-competent (C57BL/10ScSn) mice demonstrated that parasite loads are significantly higher in the TLR4-deficient mice during infection.…”

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confidence: 72%

Chemokine Gene Expression in Toll-Like Receptor-Competent and -Deficient Mice Infected with Leishmania major

Antoniazi

Price

Kropf³

et al. 2004

Infect Immun

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We studied the expression of a subset of chemokines, including RANTES/CCL5, MIP-1␣/CCL3, IP-10/ CXCL10, and MCP-1/CCL2, in Toll-like receptor (TLR)-competent and -deficient mice after infection with Leishmania major. Chemokine expression at the site of infection (the footpad), in the draining lymph nodes and in the spleens of infected animals was determined by using two different methods of analysis. The results indicate that L. major infection causes overall upregulation of RANTES/CCL5, MIP-1␣/CCL3, IP-10/CXCL10, and MCP-1/CCL2 in the footpads and lymph nodes, while expression of these chemokines is constitutive in the spleens of TLR4-competent mice (C57BL/10ScSn) and TLR4-deficient mice (C57BL10/ScN). Different patterns of expression were detected depending on the time postinfection, but there was little variation in the expression of these four chemokines in the presence or absence of TLR4.

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confidence: 72%

Chemokine Gene Expression in Toll-Like Receptor-Competent and -Deficient Mice Infected with Leishmania major

Antoniazi

Price

Kropf³

et al. 2004

Infect Immun

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“…The inhibition of NO secretion by IFN-c-primed macrophages treated with siRNA for either TLR3 or IRAK-1 may thus account for the inhibition of killing of L. donovani promastigotes by these cells. Interestingly, it was recently shown in vivo that TLR4 controls L. major replication via the induction of iNOS [30,54].…”

Section: Discussionmentioning

confidence: 99%

RNA interference reveals a role for TLR2 and TLR3 in the recognition of Leishmania donovani promastigotes by interferon–γ‐primed macrophages

2006

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Leishmania donovani promastigotes evade the induction of a proinflammatory response during their invasion of naive macrophages. However, their entry into IFN-c-primed macrophages is accompanied by the secretion of nitric oxide (NO) and proinflammatory cytokines. In the present study, we addressed the hypothesis that priming with IFN-c induces the expression of a receptor that enables mouse macrophages to recognize L. donovani promastigotes. We observed that in IFN-c-primed macrophages, L. donovani promastigotes stimulated Interleukin-1 receptor-associated kinase-1 (IRAK-1) activity. We next showed that Toll-like receptor (TLR)3 is barely detectable in naive macrophages but is expressed in IFN-c-treated macrophages. Silencing of TLR3, TLR2, IRAK-1 and myeloid differentiation factor 88 (MyD88) expression by RNA interference revealed that both TLR are involved in the secretion of NO and TNF-a induced by L. donovani promastigotes. Using L. donovani mutants, we showed that TLR2-mediated responses are dependent on Galb1,4Mana-PO 4 -containing phosphoglycans, whereas TLR3-mediated responses are independent of these glycoconjugates. Furthermore, our data indicate a participation of TLR2 and TLR3 in the phagocytosis of L. donovani promastigotes and a role for TLR3 in the leishmanicidal activity of the IFN-c-primed macrophages. Collectively, our data are consistent with a model where recognition of L. donovani promastigotes depends on the macrophage activation status and requires the expression of TLR3.

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“…In our study, TLR2 was expressed only by macrophage in the double immunostaining. Macrophage is the most important cell in the cutaneous leishmaniasis and several studies demonstrated that TLR2 is expressed at the surface of this cell 6,8,12,13 . The absence of TLR2 in other cells can be associated with the phase of the disease, because DC and NK cells decrease in this period of the leishmaniasis.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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Infection of C57BL/10ScCr and C57BL/10ScNCr mice withLeishmania majorreveals a role for Toll-like receptor 4 in the control of parasite replication

Cited by 78 publications

References 75 publications

Chemokine Gene Expression in Toll-Like Receptor-Competent and -Deficient Mice Infected with Leishmania major

Chemokine Gene Expression in Toll-Like Receptor-Competent and -Deficient Mice Infected with Leishmania major

RNA interference reveals a role for TLR2 and TLR3 in the recognition of Leishmania donovani promastigotes by interferon–γ‐primed macrophages

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

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