House Dust Mite Aeroallergen Suppresses Leukocyte Phagocytosis and Netosis Initiated by Pneumococcal Lung Infection

• Published in: Frontiers in pharmacology Vol. 13; p. 835848
• Main Authors: Papanicolaou, Angelica, Wang, Hao, McQualter, Jonathan, Aloe, Christian, Selemidis, Stavros, Satzke, Catherine, Vlahos, Ross, Bozinovski, Steven
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22.02.2022
• Subjects: asthma; house dust mite; NEtosis; phagocytosis; Pharmacology; Streptococcus pneumoniae; NEtosis; phagocytosis; asthma; house dust mite; Streptococcus pneumoniae
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2022.835848

Asthmatics are highly susceptible to developing lower respiratory tract infections caused by (SPN, the pneumococcus). It has recently emerged that underlying allergic airway disease creates a lung microenvironment that is defective in controlling pneumococcal lung infections. In the present study, we examined how house dust mite (HDM) aeroallergen exposure altered immunity to acute pneumococcal lung infection. Alveolar macrophage (AM) isolated from HDM-exposed mice expressed alternatively activated macrophage (AAM) markers including YM1, FIZZ1, IL-10, and ARG-1. , prior HDM exposure resulted in accumulation of AAMs in the lungs and 2-log higher bacterial titres in the bronchoalveolar (BAL) fluid of SPN-infected mice (Day 2). Acute pneumococcal infection further increased the expression of IL-10 and ARG1 in the lungs of HDM-exposed mice. Moreover, prior HDM exposure attenuated neutrophil extracellular traps (NETs) formation in the lungs and dsDNA levels in the BAL fluid of SPN-infected mice. In addition, HDM-SPN infected animals had significantly increased BAL fluid cellularity driven by an influx of macrophages/monocytes, neutrophils, and eosinophils. Increased lung inflammation and mucus production was also evident in HDM-sensitised mice following acute pneumococcal infection, which was associated with exacerbated airway hyperresponsiveness. Of note, PCV13 vaccination modestly reduced pneumococcal titres in the BAL fluid of HDM-exposed animals and did not prevent BAL inflammation. Our findings provide new insights on the relationship between pneumococcal lung infections and allergic airways disease, where defective AM phagocytosis and NETosis are implicated in increased susceptibility to pneumococcal infection.