Brucella induces M1 to M2 polarization of macrophages through STAT6 signaling pathway to promote bacterial intracellular survival. (July 2022)

• Record Type: Journal Article
• Authors: Wang, Yueli; Xi, Jing; Yi, Jihai; Meng, Chuang; Zhao, Xiaoli; Sun, Zhihua; Zhang, Huan; Deng, Xiaoyu; Ma, Zhongchen; Li, Honghuan; Wang, Yong; Chen, Chuangfu
• Is Part Of: Research in veterinary science. Volume 145(2022)
• Page Start: 91
• Page End: 101
• Publication Date: 2022-07
• Subjects: Brucella -- Persistent infection -- Macrophage polarization -- STAT6 signal pathway -- Survival; Veterinary medicine -- Periodicals; Veterinary Medicine -- Periodicals; Médecine vétérinaire -- Périodiques; Médecine vétérinaire -- Recherche -- Périodiques; Diergeneeskunde; 636.089
• DOI: 10.1016/j.rvsc.2022.02.006
• Languages: English
• ISSNs: 0034-5288

Abstract

Abstract: Brucella are serious intracellular pathogens that parasitize macrophages and cause persistent infection in humans and animals. Although macrophages are an important bridge between natural and acquired immunity, their role in Brucella infection is not completely clear. Recently, studies have reported that Brucella can induce macrophage polarization, although the specific molecular mechanism involved is not known. Therefore, in the current study the replication ability of Brucella melitensis strain M5 ( Brucella M5) was examined as well as its macrophage polarization and cytokine production, in a host. The role of Signal transducers and activators of transcription 6 (STAT6) in macrophage polarization induced by Brucella infection was also investigated. The results showed that Brucella M5 survived in vivo for a prolonged period of time and caused damage to the spleen and uterus tissues. The expression of type M2 cytokines was induced after Brucella M5 infection. Immunohistochemistry showed that STAT6 was upregulated in spleen and uterus tissues. At the cellular level, Brucella M5 induced macrophage transformation from M1 to M2-type during the later stage of infection. When STAT6 was silenced, the polarization of M2-type was inhibited, and the intracellular survival rate of Brucella decreased significantly. In conclusion, these findings demonstrate that STAT6 is the key factor regulates M2 polarization of macrophages and promotes the intracellular survival of Brucella in the late stage of infection and provides an explanation of the mechanism responsible for persistent Brucella infection. Highlights: Brucella M5 stimulate M0 macrophages to M1 polarization during the early stage of infection. Brucella M5 can induce transformation of M1 to M2 macrophages during the later stage of infection by STAT6 pathway The activation of the STAT6 pathway is the key factor in macrophage polarization, and it is important in promoting the intracellular survival of Brucella and inducing chronic infection.