Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
J Cell Sci. 2011 Sep 15;124(Pt 18):3041-51. doi: 10.1242/jcs.086413.
An innate immune cell can sense a pathogen, either from a distance by recognizing chemoattractant stimuli or by direct physical contact. The pathogen is subsequently neutralized, which usually occurs through its phagocytic internalization. By investigating chemotaxis and phagocytosis from an immunophysical single-cell perspective, it now appears that the demarcation between these two processes is less distinct than originally thought. Several lines of evidence support this notion. First, chemotactic stimulation does not cease at the moment of initial contact between the cell and the pathogenic target. Second, even when classical chemotaxis of neutrophils is suppressed, the early cell response to contact with typical chemoattractant targets, such as zymosan, fungal spores or chemokine-coated particles, can still involve morphological attributes of chemotaxis. Recognizing that the changing morphology of motile cells is inextricably linked to physical cell behavior, this Commentary focuses on the mechanical aspects of the early response of innate immune cells to chemotactic and phagocytic stimuli. On the basis of this perspective, we propose that the combined study of chemotaxis and phagocytosis will, potentially, not only advance our grasp of the mechanisms underlying immune-cell motility but also open new lines of research that will promote a deeper understanding of the innate recognition of pathogens.
先天免疫细胞可以感知病原体,既可以通过识别趋化刺激物远距离感知,也可以通过直接物理接触感知。随后,病原体被中和,这通常通过吞噬作用内化来实现。通过从免疫物理单细胞的角度研究趋化性和吞噬作用,现在看来,这两个过程之间的界限并不像最初想象的那么明显。有几条证据支持这一观点。首先,趋化刺激在细胞与病原体靶标最初接触时不会停止。其次,即使抑制中性粒细胞的经典趋化作用,细胞与典型趋化剂靶标(如酵母聚糖、真菌孢子或趋化因子包被的颗粒)接触后的早期细胞反应仍可能涉及趋化性的形态特征。认识到运动细胞的形态变化与物理细胞行为密不可分,本评论重点关注先天免疫细胞对趋化和吞噬刺激的早期反应的力学方面。基于这一观点,我们提出,趋化性和吞噬作用的联合研究不仅将提高我们对免疫细胞运动机制的理解,还将开辟新的研究路线,促进对病原体先天识别的更深入理解。