During the final 8 weeks, mice were challenged with 10 ng of Staphylococcal enterotoxin B (SEB; Product# 122; List Biological Laboratories Inc., Campbell, CA, USA), diluted in 1× PBS, immediately after the instillation of 3% OVA.
- were coupled to SeroMap beads using the protein quantities and buffer conditions pre- viously described.30 Tetanus toxoid (Massachusetts Biological Laboratories, Boston, MA), diphtheria toxoid from Corynebacterium diph- theriae (List Biological Laboratories, Campbell
Accurate and cost-effective identification of areas where co-endemic infections occur would enable public health managers to identify opportunities for implementation of integrated control programs. Dried blood spots collected during cross-sectional lymphatic filariasis surveys in coastal Kenya were used for exploratory integrated detection of IgG antibodies against antigens from several parasitic infections (Wuchereria bancrofti, Schistosoma mansoni, Plasmodium spp., Ascaris lumbricoides, and Strongyloides stercoralis) as well as for detection of responses to immunizing agents used against vaccine-preventable diseases (VPDs) (measles, diphtheria, and tetanus) using a multiplex bead assay (MBA) platform. High heterogeneity was observed in antibody responses by pathogen and antigen across the sentinel sites. Antibody seroprevalence against filarial antigens were generally higher in Ndau Island (P < 0.0001), which also had the highest prevalence of filarial antigenemia compared with other communities. Antibody responses to the Plasmodium species antigens CSP and MSP-119 were higher in Kilifi and Kwale counties, with Jaribuni community showing higher overall mean seroprevalence (P < 0.0001). Kimorigo community in Taita-Taveta County was the only area where antibody responses against S. mansoni Sm25 recombinant antigen were detected. Seroprevalence rates to Strongyloides antigen NIE ranged between 3% and 26%, and there was high heterogeneity in immune responses against an Ascaris antigen among the study communities. Differences were observed between communities in terms of seroprevalence to VPDs. Seroprotection to tetanus was generally lower in Kwale County than in other counties. This study has demonstrated that MBA holds promise for rapid integrated monitoring of trends of infections of public health importance in endemic areas.
IQGAP1 restrains T‐cell cosignaling mediated by OX40
- Freund's adjuvant (CFA) emulsion containing 400 μg Mycobacterium tuberculosis (Difco Laboratories, Detroit, MI, USA), into wild-type or Iqgap1−/− B6 mice on day 0. The mice received intraperitoneal injection of 200 ng per- tussis toxin (List Biological Laboratories
A costimulatory signal from the tumor necrosis factor receptor (TNFR) family molecule OX40 (CD134), which is induced on activated T cells, is important for T‐cell immunity. Aberrant OX40 cosignaling has been implicated in autoimmune and inflammatory disorders. However, the molecular mechanism by which the OX40 cosignaling regulates the T‐cell response remains obscure. We found that OX40 associated with a scaffold protein, IQ motif‐containing GTPase‐activating protein 1 (IQGAP1) after ligation by its ligand OX40L. Naïve CD4+ T cells from Iqgap1−/− mice displayed enhanced proliferation and cytokine secretion upon receiving OX40 cosignaling. A C‐terminal IQGAP1 region was responsible for its association with OX40, and TNFR‐associated factor 2 (TRAF2) bridged these two proteins. The enhanced cytokine response in Iqgap1−/− T cells was restored by the expression of the C‐terminal IQGAP1. Thus, the IQGAP1 binding limits the OX40 cosignaling. Disease severity of experimental autoimmune encephalomyelitis (EAE) was significantly exacerbated in Iqgap1−/− mice as compared to wild‐type mice. Additionally, recipient mice with Iqgap1−/− donor CD4+ T cells exhibited significantly higher EAE scores than those with their wild‐type counterparts, and OX40 blockade led to a significant reduction in the EAE severity. Thus, our study defines an important component of the OX40 cosignaling that restricts inflammation driven by antigen‐activated T cells.
Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Myelin Regeneration in an Animal Model of Multiple Sclerosis
At day 0, each mouse received two subcutaneous injections of the MOG solution as well as a 100 µl dose of 2 ng/µl pertussis toxins and virulence factors (List Biological Laboratories Inc., Campbell, CA, USA) diluted in sterile PBS (Thermo Fisher Scientific).
Mesenchymal stem/stromal cells (MSCs) display potent immunomodulatory and regenerative capabilities through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EVs). These functional properties of MSCs make them ideal candidates for the treatment of degenerative and inflammatory diseases, including multiple sclerosis (MS). MS is a heterogenous disease that is typically characterized by inflammation, demyelination, gliosis and axonal loss. In the current study, an induced experimental autoimmune encephalomyelitis (EAE) murine model of MS was utilized. At peak disease onset, animals were treated with saline, placenta-derived MSCs (PMSCs), as well as low and high doses of PMSC-EVs. Animals treated with PMSCs and high-dose PMSC-EVs displayed improved motor function outcomes as compared to animals treated with saline. Symptom improvement by PMSCs and PMSC-EVs led to reduced DNA damage in oligodendroglia populations and increased myelination within the spinal cord of treated mice. In vitro data demonstrate that PMSC-EVs promote myelin regeneration by inducing endogenous oligodendrocyte precursor cells to differentiate into mature myelinating oligodendrocytes. These findings support that PMSCs' mechanism of action is mediated by the secretion of EVs. Therefore, PMSC-derived EVs are a feasible alternative to cellular based therapies for MS, as demonstrated in an animal model of the disease.