Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia.
Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia.
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DOI：
10.1136/thoraxjnl-2015-208050
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发表时间：
2016-07
期刊：
影响因子：
10
通讯作者：
Simpson AJ
中科院分区：
文献类型：
--
作者：
Nolan TJ;Gadsby NJ;Hellyer TP;Templeton KE;McMullan R;McKenna JP;Rennie J;Robb CT;Walsh TS;Rossi AG;Conway Morris A;Simpson AJ
呼吸机获得性肺炎（VAP）仍然是重症监护室（ICU）中的一个重大问题。越来越多的人认识到危重病引起的免疫轻瘫对VAP发病机制的影响，但其机制仍不完全清楚。我们假设，由于常规检测的局限性，支原体科在VAP患者中比以前认识到的更普遍，并且这些生物体可能损害免疫细胞功能。从12个英国ICU招募了159名患者。所有患者均怀疑VAP，并接受支气管镜检查和支气管肺泡灌洗（BAL）。VAP被定义为在常规培养中生物体以>104菌落形成单位/ml的BAL流体生长。对样本进行支原体科（支原体和脲原体属）检测。通过PCR，并对阳性样品进行物种形成测序。36例健康献血员行BAL。此外，将健康供体单核细胞和巨噬细胞暴露于唾液支原体，并评估其对脂多糖的反应和进行吞噬的能力。支原体科在VAP患者中的检出率为49%（95%CI 33%~ 65%），而在非VAP患者中的检出率为14%（95%CI 9%~ 25%）。无菌BAL液患者的患病率与健康供体BAL液相似（10%（95% CI 4%-20%）vs 8%（95% CI 2%-22%））。最常见的微生物是M。唾液腺来自健康志愿者的血液单核细胞与M.唾液显示TNF-α对脂多糖的反应受损（p=0.0003），单核细胞源性巨噬细胞（MDM）也是如此（p=0.024）。MDM暴露于M。唾液显示吞噬功能受损（p=0.005）。这项研究表明，支原体科的VAP患者中的患病率很高，与一个明显较低的患病率在疑似VAP患者中，随后的文化反驳了诊断。最常见的微生物是M.唾液腺，能够改变关键免疫细胞的功能。支原体科可能参与VAP的发病。
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. 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. 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). 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.