生长培养基中的细菌分泌物刺激了小鼠的呼吸先天免疫反应。

Bacterial secretions in growth medium stimulate the mouse respiratory innate immune response.

机构信息

Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq.

出版信息

J Med Microbiol. 2022 Oct;71(10). doi: 10.1099/jmm.0.001588.

DOI:10.1099/jmm.0.001588

Abstract

Finding a safe innate immune response stimulator is one of the greatest challenges facing immunologists and vaccine manufacturers. The role of sterile bacterial secretions (SBSs) of in stimulating the innate immune response was not investigated previously. The comparative effect of SBSs and bacterial cells of isolates isolated from freshwater (PAE) and infected wounds (PAC) on the respiratory tract innate immune response. Four test mice groups were instilled intranasally (i.n.) with 10 c.f.u of PAC, 10 c.f.u of PAE, SBS of PAC, and SBS of PAE. Two control groups were given i.n. either LB broth or PBS. Time-course changes in IL-1 beta mRNA, TNF-alpha mRNA, IL-1β and TNF-α, leukocyte count, bacterial uptake, and intracellular bacterial killing by mouse alveolar macrophages (AMs) and histological changes were examined. Lung bacterial burdens were counted in first and second test groups. The maximum level of IL-1β was seen as early as 2 h (1360±180 pg ml) post-instillation (i.n.) with SBS of PAC and 1 h (1910±244 pgml) post-instillation with SBS of PAE. The maximum level of TNF-α was seen as early as 4 h (953±192 pg ml) post-instillation with SBS of PAC and (1197±298 pg ml) post-instillation with SBS of PAE. These values were almost in line with IL-1β and TNF-α gene expression. Moderate infiltration of leukocytes in bronchoalveolar lavage (BAL) and lung sections and moderate activity of AMs (bacterial uptake and bacterial killing) were observed. The above innate immune response parameters in mice instilled i.n. with PAC and PAE were higher (<0.05) than in the mice groups instilled i.n. with SBSs. The PAC was persistent in the lungs of mice for up to 72 h (3.5±0.22 log of c.f.u. g) and up to 48 h (2.05±0.21 log of c.f.u. g) for PAE. The administration of mice with SBS i.n. stimulates cellular and molecular arms of the innate immune response in the respiratory tract, opening the door to the possibility of using SBS of as an adjuvant.

摘要

寻找一种安全的固有免疫反应刺激剂是免疫学家和疫苗制造商面临的最大挑战之一。以前没有研究过无菌细菌分泌物（SBS）在刺激固有免疫反应中的作用。本研究比较了来自淡水（PAE）和感染伤口（PAC）的分离株的 SBS 和细菌细胞对呼吸道固有免疫反应的影响。将 4 组试验小鼠分别经鼻腔内（i.n.）滴注 10 c.f.u 的 PAC、10 c.f.u 的 PAE、PAC 的 SBS 和 PAE 的 SBS。另外 2 组对照组分别给予 i.n. LB 肉汤或 PBS。检测 IL-1β mRNA、TNF-α mRNA、IL-1β 和 TNF-α、白细胞计数、细菌摄取和肺泡巨噬细胞（AMs）的细胞内细菌杀伤以及组织学变化的时程变化。在第一和第二实验组中计数肺部细菌负荷。PAC 的 SBS 在注入后 2 小时（1360±180 pg/ml）达到 IL-1β 的最大水平，PAE 的 SBS 在注入后 1 小时（1910±244 pg/ml）达到 IL-1β 的最大水平。PAC 的 SBS 在注入后 4 小时（953±192 pg/ml）达到 TNF-α 的最大水平，PAE 的 SBS 在注入后 4 小时（1197±298 pg/ml）达到 TNF-α 的最大水平。这些值与 IL-1β 和 TNF-α 基因表达几乎一致。在支气管肺泡灌洗液（BAL）和肺切片中观察到白细胞中度浸润和 AMs （细菌摄取和细菌杀伤）中度活性。与注入 SBS 的小鼠相比，注入 PAC 和 PAE 的小鼠的上述固有免疫反应参数更高（<0.05）。PAC 在小鼠肺部的持续时间长达 72 小时（3.5±0.22 log c.f.u./g），PAE 长达 48 小时（2.05±0.21 log c.f.u./g）。通过鼻腔内给予 SBS 刺激呼吸道固有免疫反应的细胞和分子臂，为使用作为佐剂提供了可能性。