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Human genetics of life-threatening influenza pneumonitis.


  • 影响因子:4.34
  • DOI:10.1007/s00439-019-02108-3
  • 作者列表:"Zhang Q
  • 发表时间:2020-06-01

:Influenza viruses infect millions of people around the globe annually, usually causing self-limited upper respiratory tract infections. However, a small but non-negligible proportion of patients suffer from life-threatening pulmonary disease. Those affected include otherwise healthy individuals, and children with primary infections in particular. Much effort has been devoted to virological studies of influenza and vaccine development. By contrast, the enormous interindividual variability in susceptibility to influenza has received very little attention. One interesting hypothesis is that interindividual variability is driven largely by the genetic makeup of the infected patients. Unbiased genomic approaches have been used to search for genetic lesions in children with life-threatening pulmonary influenza. Four monogenic causes of severe influenza pneumonitis-deficiencies of GATA2, IRF7, IRF9, and TLR3-have provided evidence that severe influenza pneumonitis can be genetic and often in patients with no other severe infections. These deficiencies highlight the importance of human type I and III IFN-mediated immunity for host defense against influenza. Clinical penetrance is incomplete, and the underlying mechanisms are not yet understood. However, human genetic studies have clearly revealed that seemingly sporadic and isolated life-threatening influenza pneumonitis in otherwise healthy individuals can be genetic.


: 流感病毒每年感染全球数百万人,通常引起自限性上呼吸道感染。然而,一小部分但不可忽略的患者患有危及生命的肺部疾病。受影响的人包括其他方面健康的人,特别是患有原发性感染的儿童。大量的努力致力于流感和疫苗开发的病毒学研究。相比之下,流感易感性的巨大个体间差异很少受到关注。一个有趣的假设是个体间的变异性主要是由受感染患者的遗传构成驱动的。无偏倚的基因组方法已被用于寻找患有危及生命的肺流感的儿童的遗传损伤。严重流感肺炎的四种单基因原因-GATA2 、IRF7 、IRF9 和TLR3-have缺乏提供了证据,表明严重流感肺炎可能是遗传的,并且通常在没有其他严重感染的患者中。这些缺陷突出了人I型和III型IFN介导的免疫对于宿主防御流感的重要性。临床penetr率是不完整的,潜在的机制尚不清楚。然而,人类遗传学研究已经清楚地表明,在其他健康个体中,看似零星和孤立的威胁生命的流感肺炎可能是遗传的。



来源期刊:Nature immunology
作者列表:["Adrover JM","Aroca-Crevillén A","Crainiciuc G","Ostos F","Rojas-Vega Y","Rubio-Ponce A","Cilloniz C","Bonzón-Kulichenko E","Calvo E","Rico D","Moro MA","Weber C","Lizasoaín I","Torres A","Ruiz-Cabello J","Vázquez J","Hidalgo A"]

METHODS::The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.

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翻译标题与摘要 下载文献
作者列表:["Yang LC","Suen YJ","Wang YH","Lin TC","Yu HC","Chang YC"]

METHODS::Pneumonia is a common respiratory infectious disease that involves the inflammation of the pulmonary parenchyma. Periodontal disease is widespread and correlated with pneumonia. However, the relationship between periodontal treatment and clinical infectious outcomes in patients with pneumonia has remained undetermined. The aim of this study was to investigate the association between periodontal treatment and the risk of pneumonia events in the Taiwanese population. A nationwide population-based cohort study was conducted using data from the Taiwanese National Health Insurance Research Database (NHIRD). A total of 49,400 chronic periodontitis patients who received periodontal treatment from 2001 to 2012 were selected. In addition, 49,400 healthy individuals without periodontal diseases were picked randomly from the general population after propensity score matching according to age, gender, monthly income, urbanization, and comorbidities. The Cox proportional hazard regression analysis was adopted to assess the hazard ratio (HR) of pneumonia between the periodontal treatment cohort and the comparison cohort. The average ages of the periodontal treatment and comparison groups were 44.25 ± 14.82 years and 44.15 ± 14.5 years, respectively. The follow up durations were 7.66 and 7.41 years for the periodontal treatment and comparison groups, respectively. We found 2504 and 1922 patients with newly diagnosed pneumonia in the comparison cohort and the periodontal treatment cohort, respectively. The Kaplan-Meier plot revealed that the cumulative incidence of pneumonia was significantly lower over the 12 year follow-up period in the periodontal treatment group (using the log-rank test, p < 0.001). In conclusion, this nationwide population-based study indicated that the patients with periodontal treatment exhibited a significantly lower risk of pneumonia than the general population.

翻译标题与摘要 下载文献
作者列表:["Ngocho JS","Horumpende PG","de Jonge MI","Mmbaga BT"]

METHODS:OBJECTIVE:To describe the treatment of community-acquired pneumonia (CAP) in children under five years in Tanzania. METHODS:Between January and December 2017, children aged 2-59 months with chest radiography-confirmed CAP were enrolled. The parents were interviewed to collect information on the patients and home-based medication. Clinical information was derived from the patient files. Nasopharyngeal swab and blood samples were collected for isolation of the causative pathogens. Swab samples were analysed by quantitative PCR whereas blood samples were tested using BacT/Alert 3D. RESULTS:Overall, 109 children with CAP were included in this analysis. Provision of care to most children was delayed (median = 4.6 days). A quarter (26.6%) were given unprescribed/leftover antibiotics at home. Only one child had positive bacterial culture. Referrals were associated with nasopharyngeal carriage of Streptococcus pneumoniae (p = 0.003) and Haemophilus influenzae (p = 0.004). Of all admitted children, more than a quarter (n = 29) did not need to be hospitalised and inappropriately received injectable instead of oral antibiotics. CONCLUSION:We found high rates of home treatment, particularly with antibiotics. Appropriate health care was delayed for most children because of home treatment. Efforts are needed at the community level to improve awareness of antimicrobial resistance.

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