Circulating neutrophil anti-pathogen dysfunction in cirrhosis

Abstract

Neutrophils are the largest population of leucocytes and are among the first cells of the innate immune system to fight against intruding pathogens. In patients with cirrhosis, neutrophils exhibit altered functionality, including changes in phagocytic ability, bacterial killing, chemotaxis, degranulation, reactive oxygen species production and NET (neutrophil extracellular trap) formation. This results in their inability to mount an adequate antibacterial response and protect the individual from infection. Prognosis and survival in patients with cirrhosis are greatly influenced by the development of infectious complications. Multidrug-resistant bacterial infections in patients with cirrhosis are currently a growing problem worldwide; therefore, alternative methods for the prevention and treatment of bacterial infections in cirrhosis are urgently needed. The prevention and treatment of neutrophil dysfunction could be a potential way to protect patients from bacterial infections. However, the reasons for changes in neutrophil function in cirrhosis are still not completely understood, which limits the development of efficient therapeutic strategies. Both cellular and serum factors have been proposed to contribute to the functional impairment of neutrophils. Herein, we review the current knowledge on features and proposed causes of neutrophil dysfunction in cirrhosis, with a focus on current knowledge gaps and limitations, as well as opportunities for future investigations in this field.

Keywords: NETs; ROS; chemotaxis; cirrhosis; neutrophils; phagocytosis.

Fig. 1

Summary of neutrophil dysfunction features in cirrhosis. Findings consistent throughout the literature are shown. Created with Biorender.com.

Fig. 2

Overview on proposed serum factors that might directly or indirectly affect neutrophil function in cirrhosis. Created with Biorender.com.

Fig. 3

Current knowledge on how bile acids affect human neutrophil function. CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; fMLF, N-Formyl-met-leu-phe; GCDCA, glycochenodeoxycholic acid; GLCA, glycolithocholic acid; GUDCA, glycoursodeoxycholic acid; LCA, lithocholica acid; RA, relative abundance in serum; ROS, reactive oxygen species; TCDCA, taurochenodeoxycholic acid; TLCA, taurolithocholica acid; total DCA, sum of deoxycholic, taurodeoxycholic and glycodeoxycholic acids; total LCA, sum of LCA, TLCA and GLCA; total CDCA, sum of CDCA, TCDCA and GCDCA; TUDCA, tauroursodeoxycholic acid; UDCA, ursodeoxycholic acid. Created with Biorender.com.