Chronic lung inflammation primes humoral immunity and augments antipneumococcal resistance

Josef Wissing,Julia D. Boehme,Sabine Stegemann-Koniszewski,Andreas Jeron,Nicole Peters,Lothar Jänsch,Andrea Autengruber,Dunja Bruder

doi:10.1038/s41598-017-05212-4

Josef Wissing, Julia D. Boehme + Show 6 more

Open Access

https://doi.org/10.1038/s41598-017-05212-4

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Abstract

Airway epithelial cells (AECs) display remarkable plasticity in response to infectious stimuli and their functional adaptations are critical for antimicrobial immunity. However, the roles of AECs and humoral mediators to host defense in non-communicable lung inflammation remain elusive. We dissected pulmonary defense against Streptococcus pneumoniae in hosts with pre-existing inflammatory conditions (SPC-HAxTCR-HA mice). Lung tissue transcriptomics and bronchoalveolar lavage fluid (BALF) proteomics revealed an induction of humoral defense mechanisms in inflamed lungs. Accordingly, besides antibacterial proteins and complement components being overrepresented in inflamed lungs, elevated polymeric immunoglobulin receptor (pIgR)-expression in AECs correlated with increased secretory immunoglobulin (SIg) transport. Consequently, opsonization assays revealed augmented pneumococcal coverage by SIgs present in the BALF of SPC-HAxTCR-HA mice, which was associated with enhanced antipneumococcal resistance. These findings emphasize the immunologic potential of AECs as well as their central role in providing antibacterial protection and put forward pIgR as potential target for therapeutic manipulation in infection-prone individuals.

Highlights

Non-communicable chronic respiratory diseases (CRDs) are multifactorial disorders with different etiologies which manifest in pulmonary structural and/or functional changes
Inflammation in SPC-HAxTCR-HA vs. SPC-HA lungs was associated with up-regulation of 285 and down-regulation of 52 transcripts separating into 4 k-means gene clusters (Fig. 1a and b)
Well in line with the established autoimmune-mediated lung inflammation in these mice, Gene Set Enrichment Analysis (GSEA) of microarray data demonstrate a significant enrichment (FDR < 5%) for genes involved in allograft rejection and inflammatory responses in SPC-HAxTCR-HA lungs (Fig. 1c, Supplementary Table S4, Supplementary Fig. S5)

Summary

Introduction

Non-communicable chronic respiratory diseases (CRDs) are multifactorial disorders with different etiologies which manifest in pulmonary structural and/or functional changes. Besides providing a fairly impermeable physical barrier against bacterial pericellular migration, epithelial cells produce antimicrobial proteins (APs)[2] They secrete complement components[3] and complement critically contributes to immunity towards respiratory bacterial infection[4]. While submucosal plasma cells produce natural, mostly dimeric, IgA5 it is still a matter of debate which B cell subsets contribute to local and systemic natural IgM levels[6] Both immunoglobulin subtypes share a common structure: the joining chain (J chain). More recent studies introduced the concept of stimulated pulmonary resistance, i.e. enhancement of antimicrobial efficacy following respiratory inflammatory priming by administration of TLR ligands or primary infection These reports suggested an enhancement of leukocyte www.nature.com/scientificreports/. Details on the mechanisms underlying improved vs. blunted antimicrobial defense in lung inflammation remain elusive

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