Streptococcus pneumoniae aminopeptidase N regulates dendritic cells that attenuates type‐2 airway inflammation in murine allergic asthma

Abstract

Background and Purpose: Epidemiological and experimental studies suggest that microbial exposure in early childhood is linked with reduced risk to suffer asthma. Thus microbial components with immunoregulatory capabilities might serve as a preventive strategy for allergic asthma. Recently, it was identified that Streptococcus pneumoniae aminopeptidase N (PepN) could suppress T cell effector function. We sought to investigate the effect of PepN on murine allergic asthma and elucidate the underlying mechanism. Experimental Approach: The effects of intranasal administration of PepN during or before sensitization were examined in ovalbumin (OVA)-induced murine allergic asthma. The roles of CD11b + dendritic cells in PepN treated OVA-induced allergic asthma were evaluated by flow cytometry, cytokines detection and adoptive transfer. Moreover, the numbers of lung type 2 innate lymphoid cells (ILC2s) were also detected. Key Results: Administration of PepN during or before sensitization attenuated type-2 airway inflammation (eosinophilia, mucus hypersecretion, Th2 cytokines production and IgE production) in allergic asthma mice. PepN reduced lung accumulation of CD11b + dendritic cells, which was accompanied by diminished dendritic cellattracting chemokine CCL20 production as well as CCL17 and CCL22, which are Th2-cell chemokines predominantly produced by CD11b + dendritic cells. Adoptive transfer of BM-derived CD11b + dendritic cells abolished the inhibitory effect of PepN on OVA-induced type-2 airway inflammation. The numbers of lung ILC2s were decreased in asthmatic mice receiving PepN. Conclusion and Implications: PepN alleviated type-2 inflammation in OVA-induced allergic asthma mice, which was mediated by regulation of lung CD11b + dendritic cells. Our study provides a novel strategy for the prevention of allergic asthma.

Muc5ac Production Inhibited by Decreased lncRNA H19 via PI3K/Akt/NF-kB in Asthma

“…After cytospin and Wright’s staining, neutrophils, eosinophils, lymphocytes, and macrophages were differentially counted under a microscope. 27 …”

CD5L attenuates allergic airway inflammation by expanding CD11chigh alveolar macrophages and inhibiting NLRP3 inflammasome activation via HDAC2

“…BALF was collected, and total and differential leucocyte counts were determined as described previously [29,30]. Enzyme-linked immunosorbent assay (ELISA) was assessed from mice as described previously [31].…”

“…The lung tissues were fixed, dehydrated, transparent, dipped in wax, embedded and sectioned. Finally, the tissue sections were dewaxed and stained with haematoxylin eosin (H&E) and Periodic Acid-Schiff (PAS) [29,32]. The inflammatory degree was measured double blind using a numerical scoring system: 0 = no inflammation; 1 = occasional cuffing with inflammatory cells; 2 = most bronchi and vessels were surrounded by a thin layer (1-2 cells); 3 = a moderate layer (3-5 cells); 4 = a thick layer (>5 cells).…”

“…The single-cell suspension of the lung was obtained as described previously [29]. Details are provided in the Methods section of Supplementary material.…”

Elevated CXCL14 in Induced Sputum Was Associated with Eosinophilic Inflammation and Airway Obstruction in Patients with Asthma

“…An important molecular mechanism of asthma airway inflammatory pathogenesis is type 2 inflammation [4], and numerous molecules have been reported to be involved in airway inflammatory pathogenesis in asthma [5][6][7][8]. In the pathogenesis of asthma, chemokines, a group of low molecular weight (mostly 8-10 kDa) polypeptides, play a major role in the recruitment and invasion of airway inflammatory cells [9][10][11][12] and are reported to be one of the main stimuli that activate signaling pathways in the epithelial inflammatory reactions in asthma [13][14][15].…”