Lead exposure induced inflammation in bursa of Fabricius of Japanese quail (C. japonica) via NF-κB pathway activation and Wnt/β-catenin signaling inhibition

Bursa of Fabricius (BF), one of primary lymphoid organ, is unique to birds. Meanwhile, lead (Pb) is well known for its high toxicology to birds. Therefore, this study aimed to examine the chronic toxic effects of lead exposure on BF in Japanese quails (C. japonica) and the underlying mechanism of lead immunotoxicity. One-week old male quails were exposed to 0 ppm, 50 ppm, 500 ppm and 1000 ppm Pb concentrations by drinking water for four weeks. The results showed that Pb accumulation in BF increased in a dose dependent way. The growth and development of BF was retarded in 500 ppm and 1000 ppm Pb groups. The number of lymphocytes was decreased and the release of immunoglobulin G and M (IgG, IgM), complement 3 and 4 (C3, C4) was inhibited by Pb exposure. Lead exposure also caused oxidative stress and increasing apoptosis in BF. Moreover, histopathological damages characterized by inflammatory hyperemia and inflammatory cell infiltration and ultrastructural injury featured by mitochondrial vacuole, cristae fracture and chromatin concentration were found in BF of 500 ppm and 1000 ppm Pb groups. Furthermore, RNA sequencing based transcriptomic analysis revealed that molecular signaling and functional pathways in BF were disrupted by lead exposure. In addition, the activation of Nuclear Factor kappa B (NF-kappa B) pathway while the inhibition of wingless integrated/catenin beta 1 (Wnt/ beta-catenin) signaling by Pb exposure were confirmed by quantitative real-time PCR (qPCR). Our study may benefit to understand potential mechanistic pathways of developmental immunotoxicology under Pb stress.