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Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia
  1. T J Nolan1,
  2. N J Gadsby2,
  3. T P Hellyer3,
  4. K E Templeton2,
  5. R McMullan4,
  6. J P McKenna5,
  7. J Rennie1,
  8. C T Robb1,
  9. T S Walsh1,
  10. A G Rossi1,
  11. A Conway Morris1,6,
  12. A J Simpson3
  1. 1MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
  2. 2Clinical Microbiology, NHS Lothian, Edinburgh, UK
  3. 3Institute of Cellular Medicine, Newcastle University, Newcastle, UK
  4. 4Centre for Infection and Immunity, Queen's University, Belfast, UK
  5. 5Department of Microbiology, Belfast Health & Social Care Trust, Belfast, UK
  6. 6Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK
  1. Correspondence to Dr A Conway Morris, Division of Anaesthesia, University of Cambridge, Box 93, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK; mozza{at}doctors.org.uk

Abstract

Background Ventilator-acquired pneumonia (VAP) remains a significant problem within intensive care units (ICUs). There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent among patients with VAP than previously recognised, and that these organisms potentially impair immune cell function.

Methods and setting 159 patients were recruited from 12 UK ICUs. All patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage (BAL). VAP was defined as growth of organisms at >104 colony forming units per ml of BAL fluid on conventional culture. Samples were tested for Mycoplasmataceae (Mycoplasma and Ureaplasma spp.) by PCR, and positive samples underwent sequencing for speciation. 36 healthy donors underwent BAL for comparison. Additionally, healthy donor monocytes and macrophages were exposed to Mycoplasma salivarium and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed.

Results Mycoplasmataceae were found in 49% (95% CI 33% to 65%) of patients with VAP, compared with 14% (95% CI 9% to 25%) of patients without VAP. Patients with sterile BAL fluid had a similar prevalence to healthy donor BAL fluid (10% (95% CI 4% to 20%) vs 8% (95% CI 2% to 22%)). The most common organism identified was M. salivarium. Blood monocytes from healthy volunteers incubated with M. salivarium displayed an impaired TNF-α response to lipopolysaccharide (p=0.0003), as did monocyte-derived macrophages (MDMs) (p=0.024). MDM exposed to M. salivarium demonstrated impaired phagocytosis (p=0.005).

Discussion and conclusions This study demonstrates a high prevalence of Mycoplasmataceae among patients with VAP, with a markedly lower prevalence among patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The most common organism found, M. salivarium, is able to alter the functions of key immune cells. Mycoplasmataceae may contribute to VAP pathogenesis.

  • Pneumonia
  • Assisted Ventilation
  • Innate Immunity
  • Bacterial Infection
  • Cytokine Biology

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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