TY - JOUR AB - Helminth infection represents a major health problem causing approximately 5 million disability-adjusted life years worldwide. Concerns that repeated anti-helminthic treatment may lead to drug resistance render it important that vaccines are developed but will require increased understanding of the immune-mediated cellular and antibody responses to helminth infection. IL-4 or antibody-activated murine macrophages are known to immobilize parasitic nematode larvae, but few studies have addressed whether this is translatable to human macrophages. In the current study, we investigated the capacity of human macrophages to recognize and attack larval stages of Ascaris suum, a natural porcine parasite that is genetically similar to the human helminth Ascaris lumbricoides. Human macrophages were able to adhere to and trap A suum larvae in the presence of either human or pig serum containing Ascaris-specific antibodies and other factors. Gene expression analysis of serum-activated macrophages revealed that CCL24, a potent eosinophil attractant, was the most upregulated gene following culture with A suum larvae in vitro, and human eosinophils displayed even greater ability to adhere to, and trap, A suum larvae. These data suggest that immune serum-activated macrophages can recruit eosinophils to the site of infection, where they act in concert to immobilize tissue-migrating Ascaris larvae. AU - Coakley, G.* AU - Volpe, B.* AU - Bouchery, T.* AU - Shah, K.* AU - Butler, A.* AU - Geldhof, P.* AU - Hatherill, M.* AU - Horsnell, W.* AU - Esser-von Bieren, J. AU - Harris, N.L.* C1 - 59092 C2 - 48569 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Immune serum-activated human macrophages coordinate with eosinophils to immobilize Ascaris suum larvae. JO - Parasite Immunol. VL - 42 IS - 7 PB - Wiley PY - 2020 SN - 0141-9838 ER - TY - JOUR AB - Previously, vaccination of cattle with Escherichia coli-expressed bovine lungworm paramyosin (EcPMY) adjuvanted with Quil A resulted in considerable reduction in worm burden and larvae shedding (Strube et al., 2015). To further evaluate the protective potential of PMY, cattle vaccination trials were performed using either E. coli- (EcPMY) or Pichia pastoris-expressed PMY (PpPMY) with different adjuvants (Matrix-Q(™) or Quil A). Combinations EcPMY+Matrix-Q(™) (trial 1), PpPMY+Matrix-Q(™) (trial 2) and PpPMY+Quil A (trial 3) were tested against challenge infections with 2000 Dictyocaulus viviparus larvae. Even though GM worm burden and larvae shedding was lower in almost all vaccinated groups, there were high variations between individuals hampering significant differences. However, in all vaccinated groups, lungworms were significantly shorter compared to those in controls. In vitro stimulation of peripheral blood mononuclear cells (PBMC) with recombinant (r)PMY revealed no significant proliferation following vaccinations or challenge infection. All vaccinated cattle showed a significant rise in specific antibodies, particularly IgG and its subclass IgG1, and detected the native lungworm PMY in immunoblots starting two weeks after the first vaccination. The use of a different rPMY-adjuvant combination or combined vaccination with additional recombinant antigens might be a promising future approach towards a new vaccine against lungworms in cattle. AU - Joekel, D.* AU - Hinse, P.* AU - Raulf, M.K.* AU - Schicht, S.* AU - Bäumer, W.* AU - Werling, D.* AU - Kremmer, E. AU - Strube, C.* C1 - 47266 C2 - 40619 SP - 614-623 TI - Vaccination of calves with yeast- and bacterial-expressed paramyosin from the bovine lungworm Dictyocaulus viviparus. JO - Parasite Immunol. VL - 37 IS - 12 PY - 2015 SN - 0141-9838 ER - TY - JOUR AB - © 2015 John Wiley & Sons Ltd. Schistosome infections are renowned for their ability to induce regulatory networks such as regulatory T cells (Treg) that control immune responses against homologous and heterologous antigens such as allergies. However, in the case of co-infections with hepatitis C virus (HCV), schistosomes accentuate disease progression and we hypothesized that expanding schistosome-induced Treg populations change their phenotype and could thereby suppress beneficial anti-HCV responses. We therefore analysed effector T cells and n/iTreg subsets applying the markers Granzyme B (GrzB) and Helios in Egyptian cohorts of HCV mono-infected (HCV), schistosome-co-infected (Sm/HCV) and infection-free individuals. Interestingly, viral load and liver transaminases were significantly elevated in Sm/HCV individuals when compared to HCV patients. Moreover, overall Treg frequencies and HeliosposTreg were not elevated in Sm/HCV individuals, but frequencies of GrzB+Treg were significantly increased. Simultaneously, GrzB+ CD8+ T cells were not suppressed in co-infected individuals. This study demonstrates that in Sm/HCV co-infected cohorts, liver disease is aggravated with enhanced virus replication and Treg do not expand but rather change their phenotype with GrzB possibly being a more reliable marker than Helios for iTreg. Therefore, curing concurrent schistosome disease could be an important prerequisite for successful HCV treatment as co-infected individuals respond poorly to interferon therapy. AU - Loffredo-Verde, E.* AU - Abdel-Aziz, I.Z.* AU - Albrecht, J. AU - El Guindy, N.M.* AU - Yacob, M.* AU - Solieman, A.S.* AU - Protzer, U. AU - Busch, D.H. AU - Layland, L.E.* AU - Prazeres da Costa, C.U.* C1 - 43215 C2 - 36318 CY - Hoboken SP - 97-104 TI - Schistosome infection aggravates HCV-related liver disease and induces changes in the regulatory T-cell phenotype. JO - Parasite Immunol. VL - 37 IS - 2 PB - Wiley-blackwell PY - 2015 SN - 0141-9838 ER -