32 research outputs found
Negative Regulation of Schistosoma japonicum Egg-Induced Liver Fibrosis by Natural Killer Cells
The role of natural killer (NK) cells in infection-induced liver fibrosis remains obscure. In this study, we elucidated the effect of NK cells on Schistosoma japonicum (S. japonicum) egg-induced liver fibrosis. Liver fibrosis was induced by infecting C57BL/6 mice with 18ā20 cercariae of S. japonicum. Anti-ASGM1 antibody was used to deplete NK cells. Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid (poly Iā¶C) was used to enhance the activation of NK cells. Results showed that NK cells were accumulated and activated after S. japonicum infection, as evidenced by the elevation of CD69 expression and IFN-Ī³ production. Depletion of NK cells markedly enhanced S. japonicum egg-induced liver fibrosis. Administration of poly Iā¶C further activated NK cells to produce IFN-Ī³ and attenuated S. japonicum egg-induced liver fibrosis. The observed protective effect of poly Iā¶C on liver fibrosis was diminished through depletion of NK cells. Disruption of IFN-Ī³ gene enhanced liver fibrosis and partially abolished the suppression of liver fibrosis by poly Iā¶C. Moreover, expression of retinoic acid early inducible 1 (RAE 1), the NKG2D ligand, was detectable at high levels on activated hepatic stellate cells derived from S. japonicum-infected mice, which made them more susceptible to hepatic NK cell killing. In conclusion, our findings suggest that the activated NK cells in the liver after S. japonicum infection negatively regulate egg-induced liver fibrosis via producing IFN-Ī³, and killing activated stellate cells
The Scientific Principles of Memory versus the Federal Rules of Evidence
Eyewitness misidentifications have contributed to many wrongful convictions. However, despite expressing high confidence at trial, eyewitnesses often make inconclusive misidentifications on the first test conducted early in a police investigation. According to a new scientific consensus, it is important to focus on the results of the first test because, if the perpetrator is not in the lineup, the test itself leaves a memory trace of the innocent suspect in the witnessās brain. Thus, all subsequent tests of the witnessās memory for the same suspect constitute tests of contaminated memory. Unfortunately, when evidence of an initial inconclusive identification is introduced at trial, the rules of evidence provide a witness with an opportunity to explain their prior inconsistent statement. In response, witnesses often provide an opinion about why they did not confidently identify the suspect on the initial test despite doing so now (e.g., āI was nervous on the first testā).However, witnesses lack expertise ināand have no awareness ofāthe subconscious mechanisms of memory contamination that have been elucidated by decades of scientific research. The combination of a sincerely held (false) memory and a believable (but erroneous) explanation for a prior inconsistent statement is often persuasive to jurors. This is a recipe for a wrongful conviction, one that has been followed many times. The Federal Rules of Evidence were enacted almost a half-century ago, and it maybe time to revisit them in light of the principles of memory that have been established since that time
Exogenous tumor necrosis factor-alpha could induce egress of
Toxoplasmaāgondii is an intra-cellular protozoan parasite that can infect almost all nucleated cells, eliciting host immune responses against infection. Host tissue damage is mainly caused by cellular lysis when T.āgondii egresses from infected cells. However, the effects of cytokines released by host immune cells on egression of T.āgondii remain elusive. This study aimed to investigate the role of tumor necrosis factor-alpha (TNF-Ī±) on the egress of T.āgondii from infected human foreskin fibroblast (HFF) cells and to elucidate the underlying mechanisms that regulate TNF-Ī±-induced egress. Using flow cytometry to count tachyzoites of T.āgondii released into cell culture medium, we found that egress of T.āgondii from infected HFF cells could be induced by 10āng/mL TNF-Ī± in a time-dependent manner. Pre-treatment of infected HFF cells with BAPTA-AM to chelate intra-parasitic calcium could greatly inhibit TNF-Ī±-induced egress. Similar results were obtained when using cytochalasin D to block parasite motility before the TNF-Ī±-induced egress assay. In addition, blocking host apoptosis by Z-VAD-FMK could decrease TNF-Ī± induced egress, while blocking necroptosis by necrostatin-1 has little impact on TNF-Ī±-induced egress. The egressed tachyzoites displayed a normal growth rate and lost no virulence. Our results suggest that host cytokines could influence the cellular lytic processes of T.āgondii, providing new insights into the relationship between host TNF-Ī± and T.āgondii pathogenesis
Exogenous tumor necrosis factor-alpha could induce egress of Toxoplasmaāgondii from human foreskin fibroblast cells
Toxoplasmaāgondii is an intra-cellular protozoan parasite that can infect almost all nucleated cells, eliciting host immune responses against infection. Host tissue damage is mainly caused by cellular lysis when T.āgondii egresses from infected cells. However, the effects of cytokines released by host immune cells on egression of T.āgondii remain elusive. This study aimed to investigate the role of tumor necrosis factor-alpha (TNF-Ī±) on the egress of T.āgondii from infected human foreskin fibroblast (HFF) cells and to elucidate the underlying mechanisms that regulate TNF-Ī±-induced egress. Using flow cytometry to count tachyzoites of T.āgondii released into cell culture medium, we found that egress of T.āgondii from infected HFF cells could be induced by 10āng/mL TNF-Ī± in a time-dependent manner. Pre-treatment of infected HFF cells with BAPTA-AM to chelate intra-parasitic calcium could greatly inhibit TNF-Ī±-induced egress. Similar results were obtained when using cytochalasin D to block parasite motility before the TNF-Ī±-induced egress assay. In addition, blocking host apoptosis by Z-VAD-FMK could decrease TNF-Ī± induced egress, while blocking necroptosis by necrostatin-1 has little impact on TNF-Ī±-induced egress. The egressed tachyzoites displayed a normal growth rate and lost no virulence. Our results suggest that host cytokines could influence the cellular lytic processes of T.āgondii, providing new insights into the relationship between host TNF-Ī± and T.āgondii pathogenesis
B1 cells protect against Schistosoma japonicum-induced liver inflammation and fibrosis by controlling monocyte infiltration.
During Schistosoma infection, lack of B cells results in more severe granulomas, inflammation, and fibrosis in the liver, but the mechanisms underlying this pathology remain unclear. This study was to clarify the mechanisms underpinning the immunomodulation of B cells in mice infected with Schistosoma japonicum (S. japonicum). We found that B cell deficiency led to aggravated liver pathology, as demonstrated by increases in the size of the egg-associated granulomas, alanine transaminase levels, and collagen deposition. Compared with infected wild-type (WT) mice, infected B cell-deficient (Ī¼MT) mice showed increased infiltration of Ly6Chi monocytes and higher levels of proinflammatory cytokines and chemokines. Furthermore, B1 cells were increased significantly in the liver of WT mice following S. japonicum infection. Adoptively transferring B1 cells, but not B2 cells, to Ī¼MT mice significantly reduced liver pathology and liver infiltration of Ly6Chi monocytes. Additionally, secretion of IL-10 from hepatic B cells increased significantly in infected WT mice and this IL-10 was mainly derived from B1 cells. Adoptively transferring B1 cells purified from WT mice, but not from IL-10-deficient mice, to Ī¼MT mice significantly reduced liver pathology and liver infiltration of Ly6Chi monocytes. These reductions were accompanied by decreases in the expression levels of chemokines and inflammatory cytokines. Taken together, these data indicated that after S. japonicum infection, an increased number of hepatic B1 cells secrete IL-10, which inhibits the expression of chemokines and cytokines and suppresses the infiltration of Ly6Chi monocytes into the liver thereby alleviating liver early inflammation and late fibrosis
Additional file 1 of Non-alcoholic fatty liver disease risk prediction model and health management strategies for older Chinese adults: a cross-sectional study
Additional file 1: Table 1. Risk factors included in Model I