Vibrio cholerae OmpU Mediates CD36-Dependent Reactive Oxygen Species Generation Triggering an Additional Pathway of MAPK Activation in Macrophages

Abstract

OmpU, one of the porins of Gram-negative bacteria Vibrio cholerae, induces TLR1/2-MyD88-NF-kB-dependent proinflammatory cytokine production by monocytes and macrophages of human and mouse origin. In this study, we report that in both the cell types, OmpU-induced proinflammatory responses involve activation of MAPKs (p38 and JNK). Interestingly, we observed that in OmpU-treated macrophages, p38 activation is TLR2 dependent, but JNK activation happens through a separate pathway involving reactive oxygen species (ROS) generation by NADPH oxidase complex and mitochondrial ROS. Further, we observed that OmpU-mediated mitochondrial ROS generation probably depends on OmpU translocation to mitochondria and NADPH oxidase-mediated ROS production is due to activation of scavenger receptor CD36. For the first time, to our knowledge, we are reporting that a Gram-negative bacterial protein can activate CD36 as a pattern recognition receptor. Additionally, we found that in OmpU-treated monocytes, both JNK and p38 activation is linked to the TLR2 activation only. Therefore, the ability of macrophages to employ multiple receptors such as TLR2 and CD36 to recognize a single ligand, as in this case OmpU, probably explains the very basic nature of macrophages being more proinflammatory than monocytes.

Targeted delivery of antibiotics to the infected pulmonary tissues using ROS-responsive nanoparticles

“…Macrophages infected with bacteria showed increased ROS generation [29]. To verify whether Oxi-αCD NPs can consume intracellular and extracellular hydrogen peroxide, the P727 isolate-infected RAW 264.7 cells were treated with blank PLGA NPs (non-ROS-responsive), blank Oxi-αCD NPs, MXF/Oxi-αCD NPs and MXF/FA-Oxi-αCD NPs.…”

A virulent Bacillus cereus strain from deep-sea cold seep induces pyroptosis in a manner that involves NLRP3 inflammasome, JNK pathway, and lysosomal rupture

“…ROS is known to be generated from several sources, including mitochondria and NADPH oxidase [ 67 ]. A previous study showed that ROS generated by both mitochondria and NADPH oxidase were involved in JNK activation in Vibrio cholerae OmpU-treated macrophages [ 68 ]. In our study, we also observed an involvement of ROS in H2-induced JNK activation and pyroptosis.…”

Mitogen-Activated Protein Kinases (MAPKs) and Enteric Bacterial Pathogens: A Complex Interplay

“…For instance, upon attaching to host enterocytes, flagellin interacts with TLR5, prompting the production of IL-8 by activating p38, c-JNK, and Erk1/2 [135]. Similarly, OmpU, another extracellular protein primarily functioning as a porin, activates proinflammatory responses by activating p38 and c-JNK MAPKs through the TLR2 receptor [136].…”