Low-pathogenicityMycoplasmaspp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia

Abstract

BackgroundVentilator-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 setting159 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.ResultsMycoplasmataceae 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 conclusionsThis 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.

The dynamics of the pulmonary microbiome during mechanical ventilation in the intensive care unit and the association with occurrence of pneumonia

“…This approach together with characterisation of the host adaptive and innate immune factors has a potential to deliver new insights into dysbiosis of the respiratory microbiome during mechanical ventilation. Such mediating effects have recently been shown for Mycoplasma species that, generally, were not considered to be pathogenic 39. Another recent study described that the relative abundance of Bacteroidales species positively correlated with a systematic inflammatory response, measured by the concentration of tumour necrosis factor α in plasma, in patients with acute respiratory distress syndrome (ARDS) 38.…”

Identification of respiratory microbiota markers in ventilator-associated pneumonia

“…Although we observed a trend of more Mycoplasma in patients with VAP, the difference did not reach statistical significance. An increased abundance of Mycoplasma in BAL fluids from patients with VAP compared with intubated controls has recently been reported [34]. However, these were mainly commensal species of Mycoplasma and not M. pneumoniae .…”

Mycoplasma contamination affects cell characteristics and decreases the sensitivity of BV2 microglia to LPS stimulation

“…Damte et al found that the expression of inflammatory factors in mouse alveolar macrophages greatly increased after exposed to intact mycoplasma hyopneumoniae protein (Damte et al 2015). Nolan et al detected the response of mycoplasma-contaminated human monocytes and macrophages to LPS stimulation and found that, cells had lower response to LPS after mycoplasma contamination, followed by reduced secretion of inflammatory factors such as IL-1b, IL-6, TNF-a, Cox2 and iNOS, and impaired phagocytic function, which meant that contamination of mycoplasma inhibited the function of macrophages (Nolan et al 2016). Zinöcker observed that mycoplasma contamination inhibited the immune-suppression function of mesenchymal stromal cells in vivo and decreased the proliferation of lymphocytes in mixed lymphocyte reaction (Zinocker et al 2011).…”

“…Unfortunately, more and more cell lines were found to be contaminated by mycoplasma in research laboratories all over the world. It is reported that mycoplasma contamination changed the characteristics, protein expression and functions of host cells, which greatly influenced research work, especially for immune cells (Hoff et al 2018;Jimbo et al 2017;Nolan et al 2016). Thus, mycoplasma contamination has become a troublesome problem (Callaway 2014).…”