Science Bite (3 min Oral Presentation) Lorne Infection and Immunity 2019

House dust mite aeroallergen challenge suppresses pneumococcal lung clearance and exacerbates type-2 inflammation (#57)

Angelica Papanicolaou 1 , Hao Wang 1 , Christian Aloe 1 , Catherine Satzke 2 3 , Ross Vlahos 1 , Steven Bozinovski 1
  1. School of Health and Biomedical Sciences, RMIT University, Bundoora, Australia
  2. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia
  3. Departent of Paediatrics, Royal Children's Hospital , Parkville, Australia

Background and Aims:

Asthma is a debilitating chronic inflammatory lung disease caused by allergic sensitisation and further complicated by lower respiratory tract infections. Streptococcus pneumoniae (the pneumococcus, Spn) is isolated during asthma exacerbations, however the relationship between pneumococcal pneumonia and allergic asthma is yet to be fully defined. This study aimed to investigate how cellular immune responses to an acute pneumococcal infection were affected in mice challenged with the aeroallergen, house dust mite (HDM).   

 

Methods:

7-week old female BALB/c mice were exposed to saline (SAL, 35ml) or HDM (25mg in 35ml saline) aeroallergen administered directly into the lungs by intranasal administration. Mice were inoculated 3 times per week over a 3-week period. Following HDM exposure, mice were infected with Streptococcus pneumoniae (EF3030, 1 x 106 CFU) via intranasal lung inoculation and euthanized 48 hours post infection. In vivo airway responsiveness to methacholine challenge was assessed using the Scireq Flexivent instrument. Pneumococcal load and inflammatory cell profiling were evaluated in the bronchoalveolar lavage fluid (BALF).

 

Results:

HDM-aeroallergen challenge caused a significant increase in total lung resistance (Rrs) and tissue dampening (G) that was further exacerbated upon Spn infection.  Mean pneumococcal loads in the BALF increased by over 2-log in HDM treated animals (p<0.0001; SAL-Spn vs HDM-Spn). Total BALF cellularity was elevated upon HDM exposure and further increased upon pneumococcal infection (p = 0.0006; HDM vs HDM-Spn). The increase in BALF cells was primarily attributed to an increase in macrophages and eosinophils, whereas neutrophil numbers were not further increased.   

 

Conclusion:

HDM aeroallergen exposure caused significant airway hyperreactivity that was worsened following acute pneumococcal lung infection. Bacterial loads were elevated in the background of HDM challenge, and type-2 inflammatory eosinophils were further increased during acute pneumococcal lung infection.