Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling

Yen, Wei-Chen; Wu, Yi-Hsuan; Wu, Chih-Ching; Lin, Hsin-Ru; Stern, Arnold; Chen, Shih-Hsiang; Shu, Jwu-Ching; Tsun-Yee Chiu, Daniel

How G6PD deficiency can disrupt immune responses has not been clearly delineated. Since G6PD plays a vital role in cellular redox homeostasis [14] , this enzyme can influence the redox microenvironment in cells leading to modulation of physiological functions [15] . NOXs are a major source of ROS [16] [17] [18] and are involved in the initiation of cell signaling to modulate inflammatory response and the antimicrobial defense in phagocytes [14, 19] . Some transcription factors, such as NF-κB and AP-1, and certain signal transduction pathway proteins, such as MAPKs, are activated by intracellular ROS to induce inflammatory signaling [20] [21] [22] . Patients with G6PD deficiency or G6PD knockdown cells are more susceptible to pathogen infections [13, 23, 24] , indicating that the immune response is affected by G6PD status.