Activation of TLR Signaling in Sensitization-Recruited Inflammatory Monocytes Attenuates OVA-Induced Allergic Asthma.

Chao Huang,Zhigang Tian,Xiaodong Zheng,Haiming Wei,Rui Sun,Yongyan Chen,Jian Wang

doi:10.3389/fimmu.2018.02591

Abstract

The activation of Toll-like receptor (TLR) signaling is widely reported to be involved in preventing the development of allergic asthma. However, the mechanism of the protective function of TLR signaling remains limited. Here, we studied the mouse model of ovalbumin (OVA)-induced allergic asthma and found that deficiency of TLR signaling or activating TLR signaling with agonist would aggravate or attenuate OVA-induced allergic asthma, respectively, and TLR signaling-mediated protective effect mainly affected the sensitization phase. After OVA/alum sensitization, neutrophils and inflammatory monocytes were recruited into peritoneal cavity and up-regulated TLRs expression. However, adoptive transfer of inflammatory monocytes but not peritoneal macrophages or neutrophils induced allergic symptoms in recipient mice after OVA challenge even without OVA/alum sensitization, and treating the inflammatory monocytes with TLR agonist in vitro before transfer could abolish this effect, indicating that recruited inflammatory monocytes played a determinant role in OVA-induced allergic asthma, and activation of TLR signaling in them could attenuate allergic symptoms. Finally, we found that activation of TLR signaling could increase the expression of T-helper (Th) 1-associated cytokines in inflammatory monocytes. Our results suggest that activation of TLR signaling in sensitization-recruited inflammatory monocytes attenuates OVA-induced allergic asthma by promoting the expression of Th1-associated cytokines.

Highlights

Allergic asthma is an airway inflammatory disease, which is orchestrated by the interaction between genetic factors and environmental antigens, including allergens, microbes, microbial products, et al [1]
Toll-like receptors (TLRs) signaling has displayed the protective function against allergic asthma under some conditions, the cellular and molecular mechanisms of the protective function of TLR signaling in allergic asthma remain controversial or limited
To confirm if TLR signaling had a protective role in our mouse model, we established OVA-induced allergic asthma in tlr2−/−, tlr4−/−, and tlr9−/− mice, and WT mice were used as the control

Summary

INTRODUCTION

Allergic asthma is an airway inflammatory disease, which is orchestrated by the interaction between genetic factors and environmental antigens, including allergens, microbes, microbial products, et al [1]. Manipulation of Th1/Th2 balance or Tregs function by using TLR agonists might be a promising approach to reach the purpose of prevention and treatment In support of this idea, the agonist of TLR9 has been applied to patients in clinical trials for the treatment of allergic asthma by switching Th2 to Th1 immune responses [18, 19]. We found that TLR signaling displayed a protective function against OVA-induced allergic asthma, and it exerted this function at the sensitization phage of OVAinduced allergic asthma. Further studies showed that recruited inflammatory monocytes in peritoneal cavity after OVA/alum sensitization played a critical role to determine the severity of OVA-induced allergic asthma. Recruited inflammatory monocytes up-regulated TLR expression, and activation of TLR signaling with agonists in inflammatory monocytes could attenuate OVA-induced allergic asthma by promoting the expression of Th1-associated cytokines

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT