Systemic Up-Regulation of TLR4 Causes Lipopolysaccharide-Induced Augmentation of Nasal Cytokine Release in Allergic Rhinitis

Abstract

Background: Allergic rhinitis is a systemic disorder, and it is clinically well recognized that it can be aggravated by infection. Activation of the innate immune system constitutes a critical element in the process. Toll-like receptors (TLRs) comprise a part of the innate immune system, and lipopolysaccharide (LPS)-induced activation of TLR4 represents bacterial-induced interactions in various model systems. The present study examines how TLR2 and TLR4 expression is affected by symptomatic allergic rhinitis, and if LPS added upon allergen affects nasal cytokine release. Methods: In patients with pollen-induced allergic rhinitis and healthy non-allergic volunteers, nasal lavage (NAL), peripheral blood and bone marrow were sampled before and during the pollen season. TLR2 and TLR4 expression was determined flow cytometrically. Changes in the TLR receptor expression pattern were evaluated by a nasal challenge with allergen followed by LPS, or vice versa. Symptoms along with cells and cytokines in NAL were analyzed. Results: TLR4 expression increased in leukocytes in NAL, peripheral blood and bone marrow during symptomatic allergic rhinitis. A similar increase was seen for TLR2 in neutrophils in blood. Nasal challenge with allergen followed by LPS augmented the release of IL-4, IL-5, IL-10, IL-13, IFN-γ and TNF-α. Conclusion: A systemic up-regulation of TLR4 in symptomatic allergic rhinitis may explain why LPS preceded by allergen increases nasal cytokine release.

Pattern‐recognition receptors in human eosinophils

“…In line with this, most recent data on the topic show no eosinophil‐activating capability of LPS 16,17,76 . Moreover, recent observations from our laboratory show that TLR4 in eosinophils is up‐regulated in patients with allergic rhinitis during the pollen season 80 …”

“…16,17,76 Moreover, recent observations from our laboratory show that TLR4 in eosinophils is up-regulated in patients with allergic rhinitis during the pollen season. 80 While one study found no evidence for TLR5 mRNA in human eosinophils, 16 another has detected the TLR5 protein using flow cytometry and Western blot. 17 The latter also demonstrates that the TLR5 ligand flagellin is capable of inducing eosinophil activation in terms of chemokine and cytokine secretion (IL-1b, IL-6, IL-8, GRO-a), superoxide generation, prolongation of eosinophil survival and activation of the adhesion system (ICAM-1, CD18, ICAM-3, L-selectin) with a subsequent increase in CCL5-induced migration.…”

A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

“…TLRs are pivotal actors in shaping the effective and healthy adaptive immunity with the development of immune deviation from the T-helper (Th) 2 to Th1 phenotype and maturation of T-reg cells [28,29]. Interestingly, the expression and function of TLRs [30,31,32,33,34] were demonstrated to be different in patients with asthma/AR as compared to healthy subjects.…”

Toll‐like receptor‐induced expression of epithelial cytokine receptors on haemopoietic progenitors is altered in allergic asthma

“…15 Furthermore, nasal challenge with allergen followed by LPS augmented the release of IL-4, IL-5, IL-10, IL-13, IFN-c and TNF-a. For example, TLR-4 expression increased in leucocytes in nasal fluid, peripheral blood and BM during symptomatic allergic rhinitis.…”

“…For example, TLR-4 expression increased in leucocytes in nasal fluid, peripheral blood and BM during symptomatic allergic rhinitis. 15 Furthermore, nasal challenge with allergen followed by LPS augmented the release of IL-4, IL-5, IL-10, IL-13, IFN-c and TNF-a. 15 In contrast, allergen challenge does not affect TLR-9 expression on blood and sputum plasmacytoid dendritic cells, but impairs IFN-a production by these cells.…”