Institute of Molecular and Clinical Immunology, Health Campus Immunology Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University, Leipziger Strasse 44, 39120, Magdeburg, Germany.
Infection Immunology, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
Sci Rep. 2019 Apr 5;9(1):5703. doi: 10.1038/s41598-019-42129-6.
Upon the onset of inflammatory responses, bacterial pathogens are confronted with altered tissue microenvironments which can critically impact on their metabolic activity and growth. Changes in these parameters have however remained difficult to analyze over time, which would be critical to dissect the interplay between the host immune response and pathogen physiology. Here, we established an in vivo biosensor for measuring the growth rates of Staphylococcus aureus (S. aureus) on a single cell-level over days in an ongoing cutaneous infection. Using intravital 2-photon imaging and quantitative fluorescence microscopy, we show that upon neutrophil recruitment to the infection site and bacterial uptake, non-lethal dampening of S. aureus proliferation occurred. This inhibition was supported by NADPH oxidase activity. Therefore, reactive oxygen production contributes to pathogen containment within neutrophils not only by killing S. aureus, but also by restricting the growth rate of the bacterium.
在炎症反应发生时，细菌病原体面临着组织微环境的改变，这可能会对其代谢活性和生长产生重大影响。然而，这些参数的变化一直难以随着时间的推移进行分析，这对于剖析宿主免疫反应和病原体生理学之间的相互作用至关重要。在这里，我们建立了一种体内生物传感器，用于在持续的皮肤感染中，在单细胞水平上测量金黄色葡萄球菌（S. aureus）的生长速率。通过活体双光子成像和定量荧光显微镜，我们发现，中性粒细胞招募到感染部位并摄取细菌后，S. aureus 的增殖会受到非致死性的抑制。这种抑制作用得到了 NADPH 氧化酶活性的支持。因此，活性氧的产生不仅通过杀死 S. aureus 来限制细菌的生长速度，而且通过限制细菌的生长速度来帮助控制中性粒细胞内的病原体。
