Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190410, Israel.
Int J Mol Sci. 2023 Jul 25;24(15):11905. doi: 10.3390/ijms241511905.
Diverse extracellular and intracellular cues activate mammalian mitogen-activated protein kinases (MAPKs). Canonically, the activation starts at cell surface receptors and continues via intracellular MAPK components, acting in the host cell nucleus as activators of transcriptional programs to regulate various cellular activities, including proinflammatory responses against bacterial pathogens. For instance, binding host pattern recognition receptors (PRRs) on the surface of intestinal epithelial cells to bacterial pathogen external components trigger the MAPK/NF-κB signaling cascade, eliciting cytokine production. This results in an innate immune response that can eliminate the bacterial pathogen. However, enteric bacterial pathogens evolved sophisticated mechanisms that interfere with such a response by delivering virulent proteins, termed effectors, and toxins into the host cells. These proteins act in numerous ways to inactivate or activate critical components of the MAPK signaling cascades and innate immunity. The consequence of such activities could lead to successful bacterial colonization, dissemination, and pathogenicity. This article will review enteric bacterial pathogens' strategies to modulate MAPKs and host responses. It will also discuss findings attempting to develop anti-microbial treatments by targeting MAPKs.
各种细胞外和细胞内的信号激活了哺乳动物丝裂原活化蛋白激酶（MAPK）。通常，激活始于细胞表面受体，并通过细胞内 MAPK 成分继续进行，在宿主细胞核内作为转录程序的激活剂，调节各种细胞活动，包括针对细菌病原体的促炎反应。例如，肠道上皮细胞表面上的宿主模式识别受体（PRR）与细菌病原体外部成分结合，触发 MAPK/NF-κB 信号级联，引发细胞因子的产生。这导致先天免疫反应，可以消除细菌病原体。然而，肠道细菌病原体通过将毒力蛋白（称为效应子）和毒素输送到宿主细胞中，进化出了复杂的机制来干扰这种反应。这些蛋白通过多种方式失活或激活 MAPK 信号级联和先天免疫的关键成分。这种活动的后果可能导致细菌成功定植、传播和致病性。本文将综述肠道细菌病原体调节 MAPK 和宿主反应的策略。还将讨论试图通过靶向 MAPK 来开发抗菌治疗的发现。
