Abstract
Asthmatics are highly susceptible to developing lower respiratory tract infections caused by Streptococcus pneumoniae (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. In vivo, 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.
Highlights
Asthma is a chronic airway inflammatory disease characterised by pathological airway remodelling that leads to variable and reversible airflow obstruction
We examined whether acute pneumococcal lung infection altered the phenotype and function of Alveolar macrophage (AM) following house dust mite (HDM) exposure
HDM sensitisation increased the expression of all four activated macrophage (AAM) markers and of note, combined HDM exposure and acute SPN infection (HDM-SPN) lead to a further increase in the relative expression of IL-10 and ARG1 compared to HDM alone-exposed mice (Figures 2D–G)
Summary
Asthma is a chronic airway inflammatory disease characterised by pathological airway remodelling that leads to variable and reversible airflow obstruction. The risk of hospitalisation by pneumonia is 2–4 times higher in asthmatics, where severe asthmatics are at even greater risk (Ekbom et al, 2019). This could be due to increased pneumococcal oropharyngeal carriage in both adults and children with asthma (Jounio et al, 2010; Esposito et al, 2016), as the pneumococcus usually infects the lungs by escaping from the upper respiratory tract (Bogaert et al, 2004). Asthmatics are regarded as a high-risk group where pneumococcal disease can be more severe Protection of such “high-risk” asthmatics through vaccination continues to be an important priority, it is unclear as to whether the efficacy of SPN vaccines is compromised in asthmatics (Sheikh et al, 2002)
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