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Neutrophils in community-acquired pneumonia: parallels in dysfunction at the extremes of age
  1. Frances Susanna Grudzinska1,
  2. Malcolm Brodlie2,
  3. Barnaby R Scholefield1,
  4. Thomas Jackson1,
  5. Aaron Scott1,
  6. David R Thickett1,
  7. Elizabeth Sapey1
  1. 1 Institute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
  2. 2 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
  1. Correspondence to Dr Frances Susanna Grudzinska, Institute of Inflammation and Ageing, University of Birmingham College of Medical and Dental Sciences, Birmingham B15 2TT, UK; F.GRUDZINSKA{at}


"Science means constantly walking a tight rope" Heinrich Rohrer, physicist, 1933. Community-acquired pneumonia (CAP) is the leading cause of death from infectious disease worldwide and disproportionately affects older adults and children. In high-income countries, pneumonia is one of the most common reasons for hospitalisation and (when recurrent) is associated with a risk of developing chronic pulmonary conditions in adulthood. Pneumococcal pneumonia is particularly prevalent in older adults, and here, pneumonia is still associated with significant mortality despite the widespread use of pneumococcal vaccination in middleand high-income countries and a low prevalence of resistant organisms. In older adults, 11% of pneumonia survivors are readmitted within months of discharge, often with a further pneumonia episode and with worse outcomes. In children, recurrent pneumonia occurs in approximately 10% of survivors and therefore is a significant cause of healthcare use. Current antibiotic trials focus on short-term outcomes and increasingly shorter courses of antibiotic therapy. However, the high requirement for further treatment for recurrent pneumonia questions the effectiveness of current strategies, and there is increasing global concern about our reliance on antibiotics to treat infections. Novel therapeutic targets and approaches are needed to improve outcomes. Neutrophils are the most abundant immune cell and among the first responders to infection. Appropriate neutrophil responses are crucial to host defence, as evidenced by the poor outcomes seen in neutropenia. Neutrophils from older adults appear to be dysfunctional, displaying a reduced ability to target infected or inflamed tissue, poor phagocytic responses and a reduced capacity to release neutrophil extracellular traps (NETs); this occurs in health, but responses are further diminished during infection and particularly during sepsis, where a reduced response to granulocyte colony-stimulating factor (G-CSF) inhibits the release of immature neutrophils from the bone marrow. Of note, neutrophil responses are similar in preterm infants. Here, the storage pool is decreased, neutrophils are less able to degranulate, have a reduced migratory capacity and are less able to release NETs. Less is known about neutrophil function from older children, but theoretically, impaired functions might increase susceptibility to infections. Targeting these blunted responses may offer a new paradigm for treating CAP, but modifying neutrophil behaviour is challenging; reducing their numbers or inhibiting their function is associated with poor clinical outcomes from infection. Uncontrolled activation and degranulation can cause significant host tissue damage. Any neutrophil-based intervention must walk the tightrope described by Heinrich Rohrer, facilitating necessary phagocytic functions while preventing bystander host damage, and this is a significant challenge which this review will explore.

  • pneumonia
  • neutrophil biology

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  • Contributors This review was planned by ES, DRT and FSG. All authors have contributed to reviewing the literature and writing of the manuscript. FSG is the overall guarantor for the content.

  • Funding FSG is funded by the National Institute for Health Research (NIHR) and The Dunhill Medical Trust. MB was funded by the Medical Research Council (MRC) Clinician Scientist Fellowship (MR/M008797/1). BS is funded by NIHR (Clinician Scientist fellowship programme). TJ has no specific funding to declare. AS is funded by the British Lung Foundation. DRT is funded by the MRC. ES is funded by NIHR, the British Lung Foundation, MRC, Wellcome Trust and Alpha 1 Foundation.

  • Competing interests MB: not related to this work: investigator-led research grants from Pfizer and Roche Diagnostics; speaker fees paid to Newcastle University from Novartis, Roche Diagnostics and TEVA. Travel expenses to educational meetings at Boehringer Ingelheim and Vertex Pharmaceuticals.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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