ABSTRACT
Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF-expressing) and anti-inflammatory (IL-10-expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a "fourth signal" that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.
Subject(s)
B-Lymphocytes , Cytokines , Encephalomyelitis, Autoimmune, Experimental , Inflammation , Multiple Sclerosis , Oxidative Phosphorylation , Animals , Multiple Sclerosis/immunology , Humans , Cytokines/immunology , Cytokines/metabolism , Mice , B-Lymphocytes/immunology , Encephalomyelitis, Autoimmune, Experimental/immunology , Inflammation/immunology , Female , Male , Mice, Inbred C57BL , Adult , Adenosine Triphosphate/metabolism , Middle AgedABSTRACT
Feline chaphamaparvovirus (FeChPV) is a new viral strain detected in Chinese Mainland in recent years. The symptoms mainly include diarrhea and bloody stool in young cats, which can lead to death in severe cases. In this study, a TaqMan-based real-time quantitative PCR (qPCR) with specific primers and TaqMan probes based on the VP1 gene sequence of FeChPV was performed to detect the virus. The established qPCR indicated that there is no cross-reaction of FeChPV with other common feline viruses. The minimum detection limit of the established qPCR method is 3.75 × 10 copies/µL, while conventional PCR is 3.75 × 103 copies/µL. The result that the proposed qPCR protocol was shown to be 100 times more sensitive than conventional PCR. The correlation coefficients exceeded 0.995, and the amplification efficiency was 98%. The difference within and between groups is less than 5%, indicating that the established method has good repeatability. The results of clinical sample detection shown that 16 positive samples were detected from 45 stool samples by the established qPCR method. The conventional PCR method only detected 3 positive samples. In conclusion, the established qPCR method is fast and effective in identifying FeChPV, with higher specificity and sensitivity. It could be used as a diagnostic tool to quantitatively detect the virus content, which is conducive to disease monitoring and epidemiological investigation.
ABSTRACT
Goose parvovirus (GPV) has garnered global attention due to its association with severe symptoms in waterfowl. However, the process underlying the global emergence and spread of GPV remains largely elusive. In this study, we illustrated the evolutionary characteristics of GPVs from a global perspective using phylogenetic analysis, recombination analysis, selection pressure analysis, and phylogeographic analysis. Our findings indicate that GPV and muscovy duck parvovirus (MDPV) diverge into two distinct branches. Within GPV, there are two classifications: classical GPV (C-GPV) and novel GPV (N-GPV), each containing three subgroups, underscoring the significant genetic diversity of GPV. Recombination analysis revealed 11 recombination events, suggesting C-GPV, N-GPV, and MDPV co-infections. Further, phylogeographic analysis revealed that China is an important exporter of GPV and that trade might serve as a potential transmission conduit. Nonetheless, a detailed understanding of its geographic transmission dynamics warrants further investigation due to the limited scope of current genomic data in our study. This study offers novel insights into the evolutionary state and spread of GPV, holding promise for informing preventive and containment strategies against GPV infection.
