Department of Pediatrics, University of Tennessee Health Sciences Center, 50 N. Dunlap St., Memphis, TN, 38103, USA.
Med Microbiol Immunol. 2014 Oct;203(5):357-64. doi: 10.1007/s00430-014-0344-3. Epub 2014 Jun 21.
Pneumonia is the leading killer of children worldwide. Here, we report that helminth-infected mice develop fatal pneumonia when challenged with Streptococcus pneumoniae. Mice were chronically infected with either the flatworm Taenia crassiceps or the roundworm Heligmosomoides polygyrus. Upon challenge with a pneumonic type 3 strain of S. pneumoniae (A66.1), the worm-infected mice developed pneumonia at a rate and to a degree higher than age-matched control mice as measured by bioluminescent imaging and lung titers. This predisposition to pneumonia appears to be specific to S. pneumoniae, as worm-infected mice did not show evidence of increased morbidity when challenged with a lethal dose of influenza virus or sublethal doses of Staphylococcus aureus or Listeria monocytogenes. The defect was also present when worm-infected mice were challenged with a type 2 sepsis-causing strain (D39); an increased rate of pneumonia, decreased survival, and increased lung and blood titers were found. Pneumococcal colonization and immunity against acute otitis media were unaffected. Anti-helminthic treatment in the H. polygyrus model reversed this susceptibility. We conclude that helminth coinfection predisposes mice to fatal pneumococcal pneumonia by promoting increased outgrowth of bacteria in the lungs and blood. These data have broad implications for the prevention and treatment for pneumonia in the developing world, where helminth infections are endemic and pneumococcal pneumonia is common.
肺炎是全球儿童的主要杀手。在这里,我们报告称,感染蠕虫的小鼠在受到肺炎链球菌挑战时会发展为致命性肺炎。小鼠被扁形虫 Taenia crassiceps 或圆形线虫 Heligmosomoides polygyrus 慢性感染。在用肺炎链球菌 3 型(A66.1)进行肺炎挑战时,与年龄匹配的对照小鼠相比,蠕虫感染的小鼠发生肺炎的速度和程度更高,这可以通过生物发光成像和肺部滴度来衡量。这种易患肺炎的倾向似乎是特定于肺炎链球菌的,因为蠕虫感染的小鼠在受到致死剂量流感病毒或亚致死剂量金黄色葡萄球菌或李斯特菌挑战时,没有表现出发病率增加的迹象。当蠕虫感染的小鼠受到导致 2 型败血症的菌株(D39)挑战时,也存在这种缺陷;发现肺炎的发生率增加,存活率降低,肺部和血液滴度增加。肺炎球菌定植和对急性中耳炎的免疫力不受影响。在 H. polygyrus 模型中进行驱虫治疗可逆转这种易感性。我们得出结论,蠕虫合并感染通过促进肺部和血液中细菌的过度生长,使小鼠易患致命性肺炎球菌肺炎。这些数据对发展中国家肺炎的预防和治疗具有广泛的意义,在这些国家,蠕虫感染流行,肺炎球菌肺炎很常见。