Clement Cecilia G, Tuvim Michael J, Evans Christopher M, Tuvin Daniel M, Dickey Burton F, Evans Scott E
Department of Pulmonary Medicine, The University of Texas M, D, Anderson Cancer Center, Houston, TX 77030, USA.
Respir Res. 2009 Jul 27;10(1):70. doi: 10.1186/1465-9921-10-70.
Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against Streptococcus pneumoniae (pneumococcal) pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria.
To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days.
We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic. The presence of allergic inflammation did not significantly alter the neutrophilic response to the lysate, and did not affect the induced bacterial killing within the lungs.
These results suggest that allergic airway inflammation neither promotes nor inhibits progression of pneumococcal lung infection in mice, nor does it influence the successful induction of stimulated innate resistance to bacteria.
宿主对呼吸道病原体的保护性反应通常以炎症为特征。然而，肺部炎症并不总是具有保护作用，甚至可能对宿主有害。我们最近报告称，通过对吸入的细菌裂解物诱导强烈的炎症性固有免疫反应，可对肺炎链球菌（肺炎球菌）肺炎提供显著保护。相反，有人提出与哮喘相关的过敏性炎症会增加患肺炎球菌疾病的易感性。本研究旨在确定预先存在的过敏性肺部炎症是否会影响肺炎球菌肺炎的进展，或降低针对细菌的保护性固有免疫的诱导能力。
为了比较不同炎症和分泌刺激对肺炎防御的影响，对经腹腔注射卵清蛋白致敏的小鼠，在暴露于卵清蛋白、ATP和/或细菌裂解物的各种吸入组合后，用吸入的肺炎球菌进行攻击。因此，在感染性攻击之前诱导过敏性炎症、粘蛋白脱颗粒和/或刺激固有抵抗力。通过在感染后立即评估肺匀浆中的细菌菌落形成单位（CFU）来评估病原体杀伤情况，通过在攻击后18小时测量支气管肺泡灌洗液中的细胞计数来评估对不同条件的炎症反应，并在7天后评估小鼠的存活率。
我们发现有或没有过敏性炎症的小鼠在存活率上没有差异，粘蛋白脱颗粒的诱导也没有改变存活率。正如我们之前发现的，用细菌裂解物处理的小鼠在7天时存活率显著提高，并且这不受过敏性炎症或粘蛋白脱颗粒的影响。过敏性炎症主要与嗜酸性粒细胞浸润有关，而裂解物诱导的反应主要是中性粒细胞性的。过敏性炎症的存在并没有显著改变对裂解物的中性粒细胞反应，也没有影响肺内诱导的细菌杀伤。
这些结果表明，过敏性气道炎症既不促进也不抑制小鼠肺炎球菌肺部感染的进展，也不影响对细菌刺激固有抵抗力的成功诱导。
