Deficiency in TLR4 impairs regulatory B cells production induced by Schistosome soluble egg antigen.

Regulatory B cells (Bregs) producing IL-10 have negative regulatory function. Several studies have shown the important roles for Toll-like receptor 2 (TLR2), TLR4, and TLR9 ligation in the development of Bregs. We have reported that Schistosome soluble egg antigen (SEA) induced the production of Bregs. However, it remains unclear whether such activation is via the TLR pathway. The present study showed that IL-10 and TLR4 mRNA expression in spleen B cells of significantly increased in C57BL/10 J mice spleen B cells following SEA stimulation. The level of secreted IL-10 and IL-10+ B cell proportion decreased in spleen B cells derived from TLR4-deficient C57BL/10ScNJ (TLR4-/-) mice following SEA or LPS stimulation compared with C57BL/10 J mice. The CD1dhiCD5+ B cells proportion decreased in spleen B cells of TLR4-/- mice following SEA stimulation compared with control mice. NF-κB, ERK, p38MAPK and JNK signal transduction inhibitors significantly suppressed IL-10 secretion in CD1dhiCD5+ B cells induced by SEA or LPS. The phosphorylation levels of IκBα, p65, ERK, JNK and p38 were increased in CD1dhiCD5+ B cell of C57BL/10 J mice treated with LPS or SEA. In conclusion, this study suggests that TLR4 plays a critical role in Bregs activation induced by SEA. And the TLR4-triggered NF-κB and MAPK pathways activation in CD1dhiCD5+ B cells stimulated with SEA. The findings elucidated the mechanism of SEA induction of CD1dhiCD5+ B cells and helped us to understand the immune regulation during Schistosoma japonicum infection.

B10 cells induced by Schistosoma japonicum soluble egg antigens modulated regulatory T cells and cytokine production of T cells.

A distinct subset of B cells, also known as regulatory B cells, can negatively regulate T cell immune responses, but the role of these cells in schistosomiasis has not been clarified. Soluble egg antigen (SEA) and soluble adult worm antigen preparation (SWAP), which are two important antigen sources during Schistosoma japonicum infection, both can induce Th1, Th2, Th17, and Treg cells and the corresponding cytokines. However, whether they can induce the production of regulatory B cells and the regulatory function of schistosome-induced regulatory B cells remains unclear. In our studies, we first analyzed the production of regulatory B cells stimulated by SEA or SWAP using flow cytometry and enzyme-linked immunosorbent assay, and observed these cells in mice immunized by SEA or SWAP. Then, B10 cells sorted by MicroBeads were co-cultured with CD4(+) T cells, and the proportion of Treg cells were detected. At the same time, the IFN-γ, IL-4, and IL-17 levels in the culture supernatant were measured. The results showed that B10 cells were preferentially induced by SEA in vitro, and B10 could also be induced in mice immunized by SEA. SEA-induced B10 cells promoted the expansion of regulatory T cells and induced IL-4 secretion, but inhibited IL-17 production. These findings reveal that the generation of B10 cells is determined by parasitic antigen, and suggest the function of B10 cell induced by SEA. This study significantly contributes to the understanding of the immune regulatory role in schistosomiasis and may help protect hosts from infection.

Relationship of serum testosterone levels with cognitive function in chronic antipsychotic-treated male patients with schizophrenia.

INTRODUCTION: Some evidence suggests that testosterone might be involved in the cognitive impairments of schizophrenia. We assessed major cognitive domains and serum testosterone levels in male long-term inpatients with schizophrenia. This study aimed to test whether testosterone in serum was abnormal in patients, and whether it was related to the cognitive impairment of schizophrenia. METHODS: Serum testosterone levels in male schizophrenics (n = 80) and normal controls (n = 40) were measured by immunoassay. All patients were assessed for performance on executive functions, sustaining and focusing of attention, memory functions, and verbal fluency using the Digit Cancellation Test (DCT), Semantic Fluency Test, Spatial Span (SS), Trail Making Test, part A (TMT-A), Block Design, and Paced Auditory Serial Addition Test. RESULTS: Serum testosterone levels in schizophrenic patients were similar to control subjects (P > 0.05). We found that serum testosterone levels were significantly correlated with total time taken (in seconds) in the DCT (r = 0.261, P < 0.05) and SS score (r = -0.240, P < 0.05) in schizophrenic patients. Moreover, backward linear regression revealed that testosterone levels significantly predicted performance in DCT (ß = 0.240, P = 0.028) and SS score (ß = -0.207, P = 0.047) in patients. DISCUSSION: Our findings suggest that there is no significant difference in serum testosterone levels between groups, and that serum testosterone levels are associated with the spatial memory and attention deficits in chronic antipsychotic-treated male patients with schizophrenia.