Conclusion

Multiple lines of investigation have revealed the importance of TLRs in the development and progression of asthma. By signaling in response to inhaled pathogens or endogenous ligands, TLRs regulate both innate and adaptive immune responses

Figure 2

Mechanisms associated with TLR-dependent regulation of inflammation TLR receptors are expressed on both antigen presenting cells as well as T-regulatory cells. Activation of TLRs can result in production of both proinflammatory or anti-inflammatory cytokines, which impact Th1/Th2 balance. IL-6 can block the suppressive activity of Tregs. Direct TLR stimulation of Tregs can both enhances suppressive activity and induces proliferation of these cells. IL-10 can enhance suppressive activity of Tregs.

Figure 2

Mechanisms associated with TLR-dependent regulation of inflammation TLR receptors are expressed on both antigen presenting cells as well as T-regulatory cells. Activation of TLRs can result in production of both proinflammatory or anti-inflammatory cytokines, which impact Th1/Th2 balance. IL-6 can block the suppressive activity of Tregs. Direct TLR stimulation of Tregs can both enhances suppressive activity and induces proliferation of these cells. IL-10 can enhance suppressive activity of Tregs.

in the lung and impact airway inflammation and hyper-reactivity. Mechanisms associated with TLR dependant regulation of inflammation in the context of Th1, Th2 and T reg function are shown in Figure 2. The effect of TLRs on asthma can be either beneficial or detrimental depending on many host factors, as well as, dose, duration, and intensity of exposure to TLR ligand. The ability of TLR agonists or antagonists to pharmacologically manipulate the immune system to prevent the development or progression of airway disease is an expanding area of investigation. Given the complexity of the asthma phenotype, it is likely that timing and dose of TLR receptor agonists/antagonists will greatly affect their impact on airway disease. While it is likely that pharmacologic TLR agonists/antagonists will alter biologic responses to inhaled antigens, they may also affect susceptibility to common pathogens and this must be carefully monitored. TLR-agonists have already been studied as adjuvants to increase efficacy of vaccinations [153-155]. Pharmacologic manipulation of the innate immune system in attempts to control airways disease will require an intricate knowledge of the biological response to inhaled TLR agonists and antagonists. It is possible that with an improved understanding of the multiple means which TLRs modify airway phenotype, we will be able to target these receptors to modify the development and progression of airways disease. The timing and biologic context of stimulation of TLRs appears to determine the response of the airways.

Acknowledgement

The authors gratefully acknowledge the National Institute for Environmental Health Sciences for support (ES12717).

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Responses

  • Fraser
    What is the conclusion on inflammation?
    10 months ago

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