Muneshwar Sharma

MS20001

Modulation of Dendritic Cell Immune Function by Vibrio cholerae Outer Membrane Protein 'OmpU'
Layman summary- An outer membrane porin protein of the human pathogen Vibrio cholerae called OmpU
helps the bacterium survive in the gut. This study shows that OmpU activates his NLRP3 inflammasome
and induces proinflammatory responses in DCs via the TLR2 pathway. It has also been observed that
OmpU translocates to dc mitochondria. We found that caused OmpU cytosolic ROS. This also helps in DCs
respond to inflammatory stimuli. Production of cytosolic ROS by DCs requires the scavenger receptor
CD36.
Scientific summary-
Background:
The outer membrane of Gram-negative bacteria contains porins. Porins are large pore-forming proteins that
can transport hydrophilic compounds between the outer medium and the periplasm. The nature of oral
transmission by Vibrio cholerae, the causative agent of cholera, means that the bacterium must adapt to
severe changes in the environment, such as: B. Acidic pH and presence of bile. Based on their localization
and regulation of expression in response to these external factors, V. cholerae OmpU and OmpT porins are
believed to be involved in bacterial adaptation to the host environment. cholera is considered a classic non-
inflammatory toxic diarrhea. Intestinal dendritic cells (DCs) are localized throughout the intestinal lamina
propria as immature cells, and DCs are recruited by chemokines to the microbial site of infection to induce
an inflammatory response. This improves bacterial survival within the gut during pathogenesis. OmpU has
also been shown to affect dendritic cell (DC) responses. DCs are the majority of antigen-presenting cells
that influence the outcome of adaptive immune responses. Through activation of both the NLRP3
inflammasome and the TLR2- signaling pathway, OmpU induces proinflammatory responses in DCs. To
further investigate the signaling cascade, we showed that OmpU induced the production of mitochondrial
ROS, leading to activation of the NLRP3 inflammasome. Further investigation indicated that one of the
factors contributing to OmpU-induced mitochondrial ROS production in DCs was calcium signaling. OmpU
translocation into mitochondria has also been shown to support the production of mitochondrial ROS.
OmpU generates cytosolic ROS that add to mitochondrial ROS.
Objective:
OmpU can modulate dendritic cell responses.
Method: Toxin produced by Vibrio cholerae elevates cAMP levels in intestinal crypt cells. OmpU activates
the NLRP3 inflammasome and induces his production of mitochondrial ROS, enabling the study of
signaling. Investigations revealed that calcium signaling is one of the factors contributing to OmpU-induced
mitochondrial ROS formation in DCs.
Results:
TLR2-mediated signaling is required for her NOX-mediated ROS production, and the scavenger receptor
CD36 also contributes significantly to her ROS production in the cytoplasm of DCs. Activation of the NOX
complex by OmpU in the MAPK JNK of DCs is proposed to be involved by further investigating downstream
signaling.
Conclusions:
OmpU also has the power to modify dendritic cell (DC) responses. DCs are the primary antigen-presenting
cells that determine the outcome of adaptive immune responses. OmpU stimulates the cytoplasm to
generate ROS and supports proinflammatory responses in DCs. To generate cytosolic ROS, OmpU
triggers NADPH oxidase (NOX).