Corticosterone reprograms splenic responses to avian pathogenic Escherichia coli infection in broiler chickens.

Abstract

The spleen is a critical secondary immune organ. Various stressors encountered during rearing can induce a stress state in poultry, leading to splenic atrophy. However, the underlying mechanisms remain poorly understood. Moreover, research on how the spleen responds to Escherichia coli (E. coli) infection under stress conditions is still limited. In this study, we established a broiler stress model by subcutaneously administrating corticosterone (CORT) solution for 7 consecutive days, followed by intramuscularly challenge with avian pathogenic Escherichia coli (APEC). The results showed that CORT treatment induced splenic atrophy in broilers. Transcriptomic analysis, combined with TUNEL and PCNA staining results, suggested that this atrophy might be attributed to increased apoptosis and decreased proliferation of spleen cells. Notably, CORT treatment resulted in a reduction in B cell numbers and an increase in the number of heterophil in spleen, indicating that CORT treatment may suppress adaptive immunity while compensatorily enhancing innate immunity to maintain immune homeostasis in spleen. Subsequently, we further examined how CORT pretreatment influenced the spleen immune response to APEC infection. APEC infecton induced splenomegaly, while no significant enlargement was observed in spleen with CORT pretreatment. Transcriptomic analysis showed that the immune response of spleen changed significantly after APEC infection, with or without CORT pretreatment. In addition, compared with APEC infection alone, CORT pretreatment followed by APEC infection resulted in splenic atrophy, with B cell reduction and increased heterophil accumulation. Notably, these heterophil exhibited enhanced antimicrobial peptides production and up-regulated phagolysosome pathways to facilitate pathogen clearance. Moreover, colony stimulating factor 3 receptor (CSF3R) and CCAAT/enhancer binding protein beta (CEBPB) may serve as key regulators in heterophil maturation, chemotaxis, and function in this process. These results indicate that CORT treatment induce splenic atrophy by inhibiting cell proliferation and promoting apoptosis, while suppressing adaptive immunity and enhancing innate immunity. APEC infection with CORT pretreatment increased heterophil numbers and activity, potentially improving pathogen clearance, CSF3R and CEBPB may contribute to this process.