Differential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages

Innate immunity

article

De Chang¹  Jingjing Feng²  Hongbo Liu²  Wei Liu²  Lokesh Sharma²  Charles S Dela Cruz² 

[1] Third Medical Center of Chinese PLA General Hospital;Section of Pulmonary, Internal Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine

关键词: Epithelial cells;    macrophage;    phagocytosis;    Akt pathway;    Klebsiella;   

DOI  :  10.1177/1753425920942582

来源: Sage Journals

【 摘 要 】

Host response to lung infection includes coordinated efforts of multiple cell types, including the lung epithelium and macrophages. Importantly, both the lung epithelium and macrophages can internalize and clear invading pathogens. However, the mechanisms and their ability to internalize or phagocytose differ. Akt is a key cellular pathway that controls cell proliferation and survival, in addition to its role in host defense. The role of the Akt pathway was assessed using pharmacological Akt modulators in lung epithelial (A549) and macrophage (RAW 264.7) cell lines during Klebsiella bacterial infection. Our data show that the inhibition of the Akt pathway using specific Akt inhibitor MK2206 increased the phagocytic ability of lung epithelial cells but not of macrophages. In contrast, the activation of Akt using specific activator SC-79 decreased the phagocytic ability of epithelial cells, while it increased the phagocytic ability of macrophages. The altered phagocytic ability in both cell types using Akt modulators was not due to changes in bacterial adhesion to the host cell. The clinical usefulness of these Akt modulators may vary based on the type of infection and on the relative contribution of epithelial cells and macrophages in clearing the particular bacterial infection. The Akt pathway has differential roles in the internalization of Klebsiella bacteria by respiratory epithelial cells and immune cells.

【 授权许可】

CC BY|CC BY-NC