Toll-Like Receptor 2 Participates in Mediation of Immune Response in Experimental Pneumococcal Meningitis

AbstractToll-like receptor 2 (TLR2) is a key member of TLRs, which is crucial in the initial inflammatory response against bacteria. TLR2, is also the initial barrier against bacterial infection and plays an important role in recognising a variety of bacterial lipoproteins. Several studies have been performed to investigate the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility. Unfortunately, the results of previous studies were controversial. Therefore, we performed a meta-analysis to derive a more precise estimation of the association. The association between the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility was assessed by odds ratios together with their 95% confidence intervals (CI). Six studies were enrolled in the present meta-analysis. Overall, no significant association between TLR2 + 2477G/A polymorphism and bacterial meningitis risk were found under allele contrast (A vs. G: OR = 1.15, 95% CI = 0.93–1.43, P = 0.202), recessive genetic model (AA vs. AG/GG: OR = 1.12, 95% CI = 0.90–1.41, P = 0.313). The significant association was found between TLR2 + 2477G/A polymorphism and pneumococcal meningitis risk under allele contrast (A vs. G: OR = 1.54, 95% CI = 1.01–2.36, P = 0.046), recessive genetic model (AA vs. AG/GG: OR = 1.63, 95% CI = 1.03–2.57, P = 0.035). We conclude that TLR2 + 2477G/A polymorphism is not associated with meningococcal meningitis risk but contributes an increased risk of pneumococcal meningitis.

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Lipophosphopeptidoglycan of Entamoeba histolytica Induces an Antiinflammatory Innate Immune Response and Downregulation of Toll-Like Receptor 2 (TLR-2) Gene Expression in Human Monocytes

Archives of Medical Research ◽

10.1016/s0188-4409(00)00199-5 ◽

2000 ◽

Vol 31 (4) ◽

pp. S71-S73 ◽

Cited By ~ 22

Author(s):

Carmen Maldonado ◽

Wendy Trejo ◽

Antonio Ramı́rez ◽

Manuel Carrera ◽

Joaquı́n Sánchez ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Entamoeba Histolytica ◽

Innate Immune Response ◽

Innate Immune ◽

Human Monocytes ◽

Toll Like Receptor ◽

Toll Like Receptor 2

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Interactions between Yersinia pestis V-antigen (LcrV) and human Toll-like receptor 2 (TLR2) in a modelled protein complex and potential mechanistic insights

BMC Immunology ◽

10.1186/s12865-019-0329-5 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Tiandi Wei ◽

Jing Gong ◽

Guojing Qu ◽

Mingyu Wang ◽

Hai Xu

Keyword(s):

Immune Response ◽

Yersinia Pestis ◽

Mechanistic Model ◽

White Blood Cells ◽

Dynamics Simulation ◽

Structure Model ◽

Toll Like Receptor ◽

Toll Like Receptor 2 ◽

V Antigen

Abstract Background Yersinia pestis, the etiological pathogen of plague, is capable of repressing the immune response of white blood cells to evade phagocytosis. The V-antigen (LcrV) was found to be involved in this process by binding to human Toll-like Receptor 2 (TLR2). The detailed mechanism behind this LcrV and TLR2 mediated immune response repression, however, is yet to be fully elucidated due to the lack of structural information. Results In this work, with protein structure modelling, we were able to construct a structure model of the heterotetramer of Y. pestis LcrV and human TLR2. Molecular dynamics simulation suggests the stability of this structure in aquatic environment. The LcrV model has a dumbbell-like structure with two globule domains (G1 at N-terminus and G2 away from membrane) connected with a coiled-coil linker (CCL) domain. The two horseshoe-shape TLR2 subunits form a V-shape structure, are not in direct contact with each other, and are held together by the LcrV homodimer. In this structure model, both the G1 and CCL domains are involved in the formation of LcrV homodimer, while all three domains are involved in LcrV-TLR2 binding. A mechanistic model was proposed based on this heterotetrameric structure model: The LcrV homodimer separates the TLR2 subunits to inhibit the dimerization of TLR2 and subsequent signal transfer for immune response; while LcrV could also inhibit the formation of heterodimers of TLR2 with other TLRs, and leads to immune response repression. Conclusions A heterotetrameric structure of Y. pestis LcrV and human TLR2 was modelled in this work. Analysis of this modelled structure showed its stability in aquatic environments and the role of LcrV domains and residues in protein-protein interaction. A mechanistic model for the role of LcrV in Y. pestis pathogenesis is raised based on this heterotetrameric structure model. This work provides a hypothesis of LcrV function, with which further experimental validation may elucidate the role of LcrV in human immune response repression.

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Toll-Like Receptor 2 Arg677Trp Polymorphism Is Associated with Susceptibility to Tuberculosis in Tunisian Patients

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.11.3.625-626.2004 ◽

2004 ◽

Vol 11 (3) ◽

pp. 625-626 ◽

Cited By ~ 145

Author(s):

Meriem Ben-Ali ◽

Mohamed-Ridha Barbouche ◽

Soufia Bousnina ◽

Abdellatif Chabbou ◽

Koussay Dellagi

Keyword(s):

Immune Response ◽

Risk Factor ◽

Nucleotide Substitution ◽

Healthy Controls ◽

Toll Like Receptor ◽

Tuberculosis Patients ◽

Tunisian Patients ◽

Toll Like Receptor 2 ◽

Arg677trp Polymorphism

ABSTRACT Toll-like receptor 2 (TLR2) is critical in the immune response to mycobacteria. Herein, we report that the frequency of a human TLR2 Arg677Trp polymorphism (C2029T nucleotide substitution) in tuberculosis patients in Tunisia is significantly higher than in healthy controls (P < 0.0001). This finding suggests that this polymorphism could be a risk factor for tuberculosis.

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MyD88‐Dependent Immune Response Contributes to Hearing Loss in Experimental Pneumococcal Meningitis

The Journal of Infectious Diseases ◽

10.1086/512859 ◽

2007 ◽

Vol 195 (8) ◽

pp. 1189-1193 ◽

Cited By ~ 20

Author(s):

Matthias Klein ◽

Caroline Schmidt ◽

Stefan Kastenbauer ◽

Robert Paul ◽

Carsten J. Kirschning ◽

...

Keyword(s):

Immune Response ◽

Hearing Loss ◽

Pneumococcal Meningitis ◽

Experimental Pneumococcal Meningitis

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Development of a Secondary Immune Response toMycobacterium tuberculosisIs Independent of Toll-Like Receptor 2

Infection and Immunity ◽

10.1128/iai.01076-10 ◽

2010 ◽

Vol 79 (3) ◽

pp. 1118-1123 ◽

Cited By ~ 11

Author(s):

Amanda McBride ◽

Kamlesh Bhatt ◽

Padmini Salgame

Keyword(s):

Immune Response ◽

T Cells ◽

Host Resistance ◽

Toll Like Receptor ◽

Response Phenotype ◽

Toll Like Receptor 2 ◽

Antigen Presenting ◽

Memory Immune Response

ABSTRACTPublished work indicates that the contribution of Toll-like receptor 2 (TLR2) to host resistance during acuteMycobacterium tuberculosisinfection is marginal. However, in these studies, TLR2 participation in the memory immune response toM. tuberculosiswas not determined. The substantialin vitroevidence thatM. tuberculosisstrongly triggers TLR2 on dendritic cells and macrophages to bring about either activation or inhibition of antigen-presenting cell (APC) functions, along with accumulating evidence that memory T cell development can be calibrated by TLR signals, led us to question the role of TLR2 in host resistance to secondary challenge withM. tuberculosis. To address this question, a memory immunity model was employed, and the response of TLR2-deficient (TLR2 knockout [TLR2KO]) mice following a secondary exposure toM. tuberculosiswas compared to that of wild-type (WT) mice based on assessment of the bacterial burden, recall response, phenotype of recruited T cells, and granulomatous response. We found that upon rechallenge withM. tuberculosis, both WT and TLR2KO immune mice displayed similarly enhanced resistance to infection in comparison to their naïve counterparts. The frequencies ofM. tuberculosis-specific gamma interferon (IFN-γ)-producing T cells, the phenotypes of recruited T cells, and the granulomatous responses were also similar between WT and TLR2KO immune mice. Together, the findings from this study indicate that TLR2 signaling does not influence memory immunity toM. tuberculosis.

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