Heliyon (Nov 2023)
Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone mediates Ca+2 dysregulation, mitochondrial dysfunction, and apoptosis in human peripheral blood lymphocytes
Abstract
N-(3-oxododecanoyl)-l-homoserine lactone is a Pseudomonas aeruginosa secreted quorum-sensing molecule that mediates the secretion of virulence factors, biofilm formation and plays a pivotal role in proliferation and persistence in the host. Apart from regulating quorum-sensing, the autoinducer signal molecule N-(3-oxododecanoyl)-l-homoserine lactone (3O–C12-HSL or C12) of a LasI–LasR circuit exhibits immunomodulatory effects and induces apoptosis in various host cells. However, the precise pathophysiological impact of C12 on human peripheral blood lymphocytes and its involvement in mitochondrial dysfunction remained largely elusive. In this study, the results suggest that C12 (100 μM) induces upregulation of cytosolic and mitochondrial Ca+2 levels and triggers mitochondrial dysfunction through the generation of mitochondrial ROS (mROS), disruption of mitochondrial transmembrane potential (ΔΨm), and opening of the mitochondrial permeability transition pore (mPTP). Additionally, it was observed that C12 induces phosphatidylserine (PS) exposure and promotes apoptosis in human peripheral blood lymphocytes. However, apoptosis plays a critical role in the homeostasis and development of lymphocytes, whereas enhanced apoptosis can cause immunodeficiency through cell loss. These findings suggest that C12 exerts a detrimental effect on lymphocytes by mediating mitochondrial dysfunction and enhancing apoptosis, which might further impair the effective mounting of immune responses during Pseudomonas aeruginosa-associated infections.
