Sanfilippo Alan M, Furuya Yoichi, Roberts Sean, Salmon Sharon L, Metzger Dennis W
Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA
Infect Immun. 2015 Jul;83(7):2976-83. doi: 10.1128/IAI.00142-15. Epub 2015 May 11.
Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected in patients with asthma and that chronic obstructive pulmonary disease (COPD), a condition similar to asthma, protects against the development of complicated pneumonia. To clarify the effects of asthma on the subsequent susceptibility to pneumococcal infection, ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced in mice followed by intranasal infection with A66.1 serotype 3 Streptococcus pneumoniae. Surprisingly, mice with ALI were significantly more resistant to lethal infection than non-ALI mice. The heightened resistance observed following ALI correlated with enhanced early clearance of pneumococci from the lung, decreased bacterial invasion from the airway into the lung tissue, a blunted inflammatory cytokine and neutrophil response to infection, and enhanced expression of transforming growth factor β1 (TGF-β1). Neutrophil depletion prior to infection had no effect on enhanced early bacterial clearance or resistance to IPD in mice with ALI. Although eosinophils recruited into the lung during ALI appeared to be capable of phagocytizing bacteria, neutralization of interleukin-5 (IL-5) to inhibit eosinophil recruitment likewise had no effect on early clearance or survival following infection. However, enhanced resistance was associated with an increase in levels of clodronate-sensitive, phagocytic SiglecF(low) alveolar macrophages within the airways following ALI. These findings suggest that, while the risk of developing IPD may actually be decreased in patients with acute asthma, additional clinical data are needed to better understand the risk of IPD in patients with different asthma phenotypes.
一般认为，哮喘会增加人类患侵袭性肺炎球菌病（IPD）的风险。然而，最近的报告表明，哮喘患者的IPD死亡率并未受到影响，并且慢性阻塞性肺疾病（COPD），一种与哮喘类似的疾病，可预防复杂性肺炎的发生。为了阐明哮喘对随后肺炎球菌感染易感性的影响，先在小鼠中诱导卵清蛋白（OVA）引起的过敏性肺部炎症（ALI），随后经鼻感染A66.1 3型肺炎链球菌。令人惊讶的是，患有ALI的小鼠对致死性感染的抵抗力明显高于非ALI小鼠。ALI后观察到的抵抗力增强与肺中肺炎球菌的早期清除增强、气道细菌向肺组织的侵袭减少、对感染的炎症细胞因子和中性粒细胞反应减弱以及转化生长因子β1（TGF-β1）的表达增强有关。感染前消耗中性粒细胞对ALI小鼠早期细菌清除增强或对IPD的抵抗力没有影响。尽管在ALI期间募集到肺中的嗜酸性粒细胞似乎能够吞噬细菌，但中和白细胞介素-5（IL-5）以抑制嗜酸性粒细胞募集同样对感染后的早期清除或存活没有影响。然而，抵抗力增强与ALI后气道内对氯膦酸盐敏感的吞噬性SiglecF（低）肺泡巨噬细胞水平增加有关。这些发现表明，虽然急性哮喘患者发生IPD的风险实际上可能降低，但需要更多临床数据来更好地了解不同哮喘表型患者的IPD风险。
