scholarly journals Growth of Yersinia pseudotuberculosis in Mice Occurs Independently of Toll-Like Receptor 2 Expression and Induction of Interleukin-10

2007 ◽  
Vol 75 (7) ◽  
pp. 3561-3570 ◽  
Author(s):  
Victoria Auerbuch ◽  
Ralph R. Isberg
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokine ◽  
Yersinia Pseudotuberculosis ◽  
Interleukin 10 ◽  
Cytokine Response ◽  
Target Cells ◽  
Toll Like Receptor ◽  
Mouse Tissues ◽  
Tnf Α ◽  
Toll Like Receptor 2

ABSTRACT Pathogenic Yersinia translocates effector proteins into target cells via a type III secretion system (TTSS), modulating the host immune response. A component of the TTSS translocon, LcrV, has been implicated in preventing inflammation through Toll-like receptor 2 (TLR2) by inducing expression of the anti-inflammatory cytokine interleukin-10 (IL-10). TLR2−/− mice were reported to be less susceptible to the enteropathogen Yersinia enterocolitica. To determine whether TLR2 also plays a role in recognition of the enteropathogen Yersinia pseudotuberculosis and whether this results in an immune response that is detrimental to the host, we evaluated the macrophage cytokine response to live Y. pseudotuberculosis and analyzed the susceptibility of TLR2−/− mice to enteropathogenic Yersinia. We find that Yersinia induction of macrophage IL-10 occurs independently of TLR2 and LcrV and is blocked by the TTSS. In particular, the TTSS effector protein YopJ, which inhibits production of the inflammatory cytokine tumor necrosis factor alpha (TNF-α), also inhibits IL-10 expression. Consistent with these results, IL-10 is undetectable in Y. pseudotuberculosis-infected mouse tissues until advanced stages of infection. In addition, we find that TLR2−/− mice (derived independently from those used in previous studies) do not display altered susceptibility to enteropathogenic Yersinia compared to wild-type mice. Tissue levels of IL-10, as well as the inflammatory cytokines TNF-α, IL-6, and gamma interferon and the chemokine macrophage chemotactic protein 1, are similar in TLR2+/+ and TLR2−/− mice during enteropathogenic Yersinia infection. Therefore, the absence of TLR2 alone does not affect the cytokine response of macrophages to, or the in vivo growth and survival of, enteropathogenic Yersinia.

scholarly journals Yersinia V–Antigen Exploits Toll-like Receptor 2 and CD14 for Interleukin 10–mediated Immunosuppression

2002 ◽  
Vol 196 (8) ◽  
pp. 1017-1024 ◽  
Author(s):  
Andreas Sing ◽  
Dagmar Rost ◽  
Natalia Tvardovskaia ◽  
Andreas Roggenkamp ◽  
Agnès Wiedemann ◽  
...  
Keyword(s):  
Immune Response ◽  
Defense Mechanisms ◽  
Cell Activation ◽  
Yersinia Pseudotuberculosis ◽  
Interleukin 10 ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2 ◽  
V Antigen ◽  
Enteropathogenic Yersinia ◽  
The Impact

A characteristic of the three human-pathogenic Yersinia spp. (the plague agent Yersinia pestis and the enteropathogenic Yersinia pseudotuberculosis and Yersinia enterocolitica) is the expression of the virulence (V)-antigen (LcrV). LcrV is a released protein which is involved in contact-induced secretion of yersinia antihost proteins and in evasion of the host's innate immune response. Here we report that recombinant LcrV signals in a CD14- and toll-like receptor 2 (TLR2)-dependent fashion leading to immunosuppression by interleukin 10 induction. The impact of this immunosuppressive effect for yersinia pathogenesis is underlined by the observation that TLR2-deficient mice are less susceptible to oral Y. enterocolitica infection than isogenic wild-type animals. In summary, these data demonstrate a new ligand specificity of TLR2, as LcrV is the first known secreted and nonlipidated virulence-associated protein of a Gram-negative bacterium using TLR2 for cell activation. We conclude that yersiniae might exploit host innate pattern recognition molecules and defense mechanisms to evade the host immune response.

scholarly journals MYCOBACTERIUM TUBERCULOSIS SISTEM IMUN ALAMIAH TERKAIT PENERIMANYA

2016 ◽  
Vol 19 (1) ◽  
pp. 45
Author(s):  
Jusak Nugraha
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokine ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Myeloid Differentiation ◽  
Toll Like Receptor ◽  
Protective Function ◽  
Adaptive Immune ◽  
Tnf Α ◽  
Myeloid Differentiation Factor

Various attemp to investigate immune response towards tuberculosis has been done in order to eradicate or to make vaccination against tuberculosis (TB) effectively. Recently it is known that innate immunity has an important role in immunity to TB despite adaptive immune response, because it was proved that adaptive immune response alone was not sufficient to eradicate this microorganism thoroughly and completely in patient’s body. After Toll-Like Receptor (TLR) was found in the end of the 20th century, many progresses has been obtained in understanding about the activation of this innate immune response. But it is still needed to understand more deeply in the immune response to M. tuberculosis to lead the development of therapy or vaccination that bring into more precise target. The activation through TLR by parts of Mycobacterium induce cytoplasm protein adaptor MyD88 (Myeloid Differentiation factor 88). MyD88 has the function to activate NF- κB and secrete pro-inflammatory cytokine such as TNF-α, IL-6, IL-12. Involvement of MyD88 is not solely dependent of TLR2 receptor and there are another pathways to induce protective function of immunocompetent cells in TB.

scholarly journals Toll-Like Receptor 2 Mediates Alveolar Macrophage Response to Pneumocystis murina

2006 ◽  
Vol 74 (3) ◽  
pp. 1857-1864 ◽  
Author(s):  
Chen Zhang ◽  
Shao-Hung Wang ◽  
Mark E. Lasbury ◽  
Dennis Tschang ◽  
Chung-Ping Liao ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Alveolar Macrophages ◽  
Nuclear Translocation ◽  
Innate Immune ◽  
Hek293 Cells ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Tnf Α ◽  
Toll Like Receptor 2

ABSTRACT The innate immune response to Pneumocystis infection is not well understood. In this study, normal C57BL/6 mouse alveolar macrophages were found to respond to Pneumocystis murina organisms through Toll-like receptor 2 (TLR2), leading to the nuclear translocation of NF-κB and the production of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) and chemokine macrophage inflammatory protein 2 (MIP-2). P. murina stimulation of normal alveolar macrophages from C57BL/6 mice resulted in increased TLR2 transcription but not increased TLR4 transcription. In gain-of-function studies with HEK293 cells expressing TLR2 or TLR4, only TLR2 was found to stimulate an NF-κB response to P. murina. TNF-α and MIP-2 production in response to P. murina by mouse alveolar macrophages was inhibited by a monoclonal antibody that specifically blocked the ligand-binding ability of TLR2. Alveolar macrophages from TLR2 knockout (TLR2−/−) mice showed little increase in TNF-α and MIP-2 mRNA levels upon P. murina stimulation. An in vivo study showed that TLR2−/− mice challenged with P. murina had reduced cytokine responses. These results indicate that TLR2 plays a major role in the innate immune response to P. murina.

scholarly journals Defective negative regulation of Toll-like receptor signaling leads to excessive TNF-α in myeloproliferative neoplasm

2019 ◽  
Vol 3 (2) ◽  
pp. 122-131 ◽  
Author(s):  
Hew Yeng Lai ◽  
Stefan A. Brooks ◽  
Brianna M. Craver ◽  
Sarah J. Morse ◽  
Thanh Kim Nguyen ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Direct Consequence ◽  
Interleukin 10 ◽  
Negative Regulation ◽  
Toll Like Receptor ◽  
Tlr Signaling ◽  
Tnf Α ◽  
Inflammatory State

Abstract Patients with myeloproliferative neoplasms (MPN) have high levels of inflammatory cytokines, some of which drive many of the debilitating constitutional symptoms associated with the disease and may also promote expansion of the neoplastic clone. We report here that monocytes from patients with MPN have defective negative regulation of Toll-like receptor (TLR) signaling that leads to unrestrained production of the inflammatory cytokine tumor necrosis factor α (TNF-α) after TLR activation. Specifically, monocytes of patients with MPN are insensitive to the anti-inflammatory cytokine interleukin 10 (IL-10) that negatively regulates TLR-induced TNF-α production. This inability to respond to IL-10 is a not a direct consequence of JAK2V617F, as the phenotype of persistent TNF-α production is a feature of JAK2V617F and wild-type monocytes alike from JAK2V617F-positive patients. Moreover, persistent TNF-α production was also discovered in the unaffected identical twin of a patient with MPN, suggesting it could be an intrinsic feature of those predisposed to acquire MPN. This work implicates sustained TLR signaling as not only a contributor to the chronic inflammatory state of MPN patients but also a potential predisposition to acquire MPN.

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