Department of Microbiology and Immunology, State University of New York at Buffalo School of Medicine, Buffalo, New York.
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts.
Cell Microbiol. 2020 Feb;22(2):e13141. doi: 10.1111/cmi.13141. Epub 2019 Nov 20.
Extracellular adenosine production is crucial for host resistance against Streptococcus pneumoniae (pneumococcus) and is thought to affect antibacterial immune responses by neutrophils. However, whether extracellular adenosine alters direct host-pathogen interaction remains unexplored. An important determinant for lung infection by S. pneumoniae is its ability to adhere to the pulmonary epithelium. Here we explored whether extracellular adenosine can directly impact bacterial adherence to lung epithelial cells. We found that signaling via A1 adenosine receptor significantly reduced the ability of pneumococci to bind human pulmonary epithelial cells. A1 receptor signaling blocked bacterial binding by reducing the expression of platelet-activating factor receptor, a host protein used by S. pneumoniae to adhere to host cells. In vivo, A1 was required for control of pneumococcal pneumonia as inhibiting it resulted in increased host susceptibility. As S. pneumoniae remain a leading cause of community-acquired pneumonia in the elderly, we explored the role of A1 in the age-driven susceptibility to infection. We found no difference in A1 pulmonary expression in young versus old mice. Strikingly, triggering A1 signaling boosted host resistance of old mice to S. pneumoniae pulmonary infection. This study demonstrates a novel mechanism by which extracellular adenosine modulates resistance to lung infection by targeting bacterial-host interactions.
细胞外腺苷的产生对于宿主抵抗肺炎链球菌（肺炎球菌）至关重要，并且被认为通过中性粒细胞影响抗菌免疫反应。然而，细胞外腺苷是否改变直接的宿主-病原体相互作用仍未得到探索。肺炎链球菌引起肺部感染的一个重要决定因素是其粘附肺上皮的能力。在这里，我们探讨了细胞外腺苷是否可以直接影响细菌对肺上皮细胞的粘附。我们发现，通过 A1 腺苷受体的信号转导显著降低了肺炎球菌与人类肺上皮细胞结合的能力。A1 受体信号通过减少血小板激活因子受体的表达来阻止细菌结合，血小板激活因子受体是肺炎球菌用于粘附宿主细胞的宿主蛋白。在体内，A1 是控制肺炎球菌肺炎所必需的，因为抑制它会导致宿主易感性增加。由于肺炎链球菌仍然是老年人社区获得性肺炎的主要原因，我们探讨了 A1 在年龄驱动的易感性感染中的作用。我们发现年轻和老年小鼠的 A1 肺表达没有差异。令人惊讶的是，触发 A1 信号增强了老年小鼠对肺炎链球菌肺部感染的宿主抵抗力。这项研究证明了细胞外腺苷通过靶向细菌-宿主相互作用来调节对肺部感染的抵抗力的新机制。
