tetano
Editor, Senior Moderator
Sci Rep. 2019 Nov 27;9(1):17732. doi: 10.1038/s41598-019-54053-w. [h=1]G-CSFR antagonism reduces neutrophilic inflammation during pneumococcal and influenza respiratory infections without compromising clearance.[/h]
Wang H[SUP]1[/SUP], Aloe C[SUP]1[/SUP], Wilson N[SUP]2[/SUP], Bozinovski S[SUP]3[/SUP].
[h=3]Author information[/h] 1 School of Health & Biomedical Sciences, RMIT University, Bundoora, 3083, Australia. 2 CSL Limited, Parkville, Victoria, 3052, Australia. 3 School of Health & Biomedical Sciences, RMIT University, Bundoora, 3083, Australia. steven.bozinovski@rmit.edu.au.
[h=3]Abstract[/h] Excessive neutrophilic inflammation can contribute to the pathogenesis of pneumonia. Whilst anti-inflammatory therapies such as corticosteroids are used to treat excessive inflammation, they do not selectively target neutrophils and may compromise antimicrobial or antiviral defences. In this study, neutrophil trafficking was targeted with a granulocyte-colony stimulating factor receptor monoclonal antibody (G-CSFR mAb) during Streptococcus pneumoniae (serotype 19F) or influenza A virus (IAV, strain HKx31) lung infection in mice. Firstly, we demonstrated that neutrophils are indispensable for the clearance of S. pneumoniae from the airways using an anti-Ly6G monoclonal antibody (1A8 mAb), as the complete inhibition of neutrophil recruitment markedly compromised bacterial clearance. Secondly, we demonstrated that G-CSF transcript lung levels were significantly increased during pneumococcal infection. Prophylactic or therapeutic administration of G-CSFR mAb significantly reduced blood and airway neutrophil numbers by 30-60% without affecting bacterial clearance. Total protein levels in the bronchoalveolar lavage (BAL) fluid (marker for oedema) was also significantly reduced. G-CSF transcript levels were also increased during IAV lung infection. G-CSFR mAb treatment significantly reduced neutrophil trafficking into BAL compartment by 60% and reduced blood neutrophil numbers to control levels in IAV-infected mice. Peak lung viral levels at day 3 were not altered by G-CSFR therapy, however there was a significant reduction in the detection of IAV in the lungs at the day 7 post-infection phase. In summary, G-CSFR signalling contributes to neutrophil trafficking in response to two common respiratory pathogens. Blocking G-CSFR reduced neutrophil trafficking and oedema without compromising clearance of two pathogens that can cause pneumonia.
PMID: 31776393 DOI: 10.1038/s41598-019-54053-w
Wang H[SUP]1[/SUP], Aloe C[SUP]1[/SUP], Wilson N[SUP]2[/SUP], Bozinovski S[SUP]3[/SUP].
[h=3]Author information[/h] 1 School of Health & Biomedical Sciences, RMIT University, Bundoora, 3083, Australia. 2 CSL Limited, Parkville, Victoria, 3052, Australia. 3 School of Health & Biomedical Sciences, RMIT University, Bundoora, 3083, Australia. steven.bozinovski@rmit.edu.au.
[h=3]Abstract[/h] Excessive neutrophilic inflammation can contribute to the pathogenesis of pneumonia. Whilst anti-inflammatory therapies such as corticosteroids are used to treat excessive inflammation, they do not selectively target neutrophils and may compromise antimicrobial or antiviral defences. In this study, neutrophil trafficking was targeted with a granulocyte-colony stimulating factor receptor monoclonal antibody (G-CSFR mAb) during Streptococcus pneumoniae (serotype 19F) or influenza A virus (IAV, strain HKx31) lung infection in mice. Firstly, we demonstrated that neutrophils are indispensable for the clearance of S. pneumoniae from the airways using an anti-Ly6G monoclonal antibody (1A8 mAb), as the complete inhibition of neutrophil recruitment markedly compromised bacterial clearance. Secondly, we demonstrated that G-CSF transcript lung levels were significantly increased during pneumococcal infection. Prophylactic or therapeutic administration of G-CSFR mAb significantly reduced blood and airway neutrophil numbers by 30-60% without affecting bacterial clearance. Total protein levels in the bronchoalveolar lavage (BAL) fluid (marker for oedema) was also significantly reduced. G-CSF transcript levels were also increased during IAV lung infection. G-CSFR mAb treatment significantly reduced neutrophil trafficking into BAL compartment by 60% and reduced blood neutrophil numbers to control levels in IAV-infected mice. Peak lung viral levels at day 3 were not altered by G-CSFR therapy, however there was a significant reduction in the detection of IAV in the lungs at the day 7 post-infection phase. In summary, G-CSFR signalling contributes to neutrophil trafficking in response to two common respiratory pathogens. Blocking G-CSFR reduced neutrophil trafficking and oedema without compromising clearance of two pathogens that can cause pneumonia.
PMID: 31776393 DOI: 10.1038/s41598-019-54053-w