Cutting Edge: Diminished T Cell TLR Expression and Function Modulates the Immune Response in Human Filarial Infection

Babu, Subash; Blauvelt, Carla P.; Kumaraswami, V.; Nutman, Thomas B.

doi:10.4049/jimmunol.176.7.3885

Cited by 117 publications

(103 citation statements)

References 14 publications

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“…The direct action of TLR9-triggered murine CD4 ϩ T cells in enhancing humoral immunity by causing increased Ig titers has also been described (42). An indirect association with human disease has also been posited through the demonstration of alterations in the expression of various TLRs on T cell subsets between healthy and ill humans during filarial (43), hepatitis C (44), and HIV (45) infections.…”

Section: Discussionmentioning

confidence: 99%

Activated Human Neonatal CD8+ T Cells Are Subject to Immunomodulation by Direct TLR2 or TLR5 Stimulation

McCarron

Reen

2009

The Journal of Immunology

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In conditions of optimal priming, the neonate possess competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonates’ natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8+ T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam3Cys (palmitoyl-3-Cys-Ser-(Lys)4) and flagellin monomers significantly enhanced proliferation, CD25+ expression, IL-2, IFN-γ, TNF-α, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8+ T cells. Blocking studies confirmed that the increase in IFN-γ production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8+ T cells to both TLR agonists had an additive effect on IFN-γ production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8+ component.

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Section: Discussionmentioning

confidence: 99%

Activated Human Neonatal CD8+ T Cells Are Subject to Immunomodulation by Direct TLR2 or TLR5 Stimulation

McCarron

Reen

2009

The Journal of Immunology

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“…TLR stimulation directly promoted IFN-c production in CD8 1 T cells. [72][73][74] Thus, the molecular mechanisms underlying TLRmediated T-cell proliferation and functional differentiation may be further explored for the treatment of chronic HBV infection.…”

Section: Activation Of Tlr-mediated Signaling Pathways Modulates Hbv-mentioning

confidence: 99%

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

Zhang

Yang

et al. 2014

Cell Mol Immunol

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It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus (HBV) infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors (TLRs) sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons (IFNs) and pro-inflammatory cytokines. Experimental results from in vitro and in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T-and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

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“…TLRs are expressed on antigen-presenting cells such as DCs, B cells, and macrophages, and on activated/memory T cells (23,24). After recognizing conserved microbial components through TLRs, cells trigger innate immune responses by producing proinflammatory cytokines and influencing TH1 and TH17 responses and antibody responses (1)(2)(3)(4)(5).…”

Section: Discussionmentioning

confidence: 99%

Modulation of TNFSF expression in lymphoid tissue inducer cells by dendritic cells activated with Toll-like receptor ligands

Han

Koo²,

Bae³

et al. 2011

BMB Reports

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Cutting Edge: Diminished T Cell TLR Expression and Function Modulates the Immune Response in Human Filarial Infection

Cited by 117 publications

References 14 publications

Activated Human Neonatal CD8+ T Cells Are Subject to Immunomodulation by Direct TLR2 or TLR5 Stimulation

Activated Human Neonatal CD8+ T Cells Are Subject to Immunomodulation by Direct TLR2 or TLR5 Stimulation

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

Modulation of TNFSF expression in lymphoid tissue inducer cells by dendritic cells activated with Toll-like receptor ligands

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