Analysis of caecal mucosal inflammation and immune modulation during Anoplocephala perfoliata infection of horses
PARASITE IMMUNOLOGY
Authors: Lawson, April L.; Pittaway, Charles E.; Sparrow, Richard M.; Balkwill, Emily C.; Coles, Gerald C.; Tilley, Alice; Wilson, A. Douglas
Abstract
Anoplocephala perfoliata is the commonest equine tapeworm, the adult parasites are attached in groups close to the ileocaecal valve causing marked inflammatory pathology. This work aimed to characterize the nature of the in vivo mucosal immune response to A perfoliata, and to investigate the role of A perfoliata excretory-secretory components in modulating in vitro immune responses. Real-time PCR detected elevation of IL13 and TGF beta transcription in early-stage A perfoliata infection. In late-stage infection, IL-13, IL4 and Ifn transcripts were reduced while the regulatory cytokines, TGF beta, IL10 and the transcription factor FOXP3 were increased in tissue close to the site of A perfoliata attachment; indicating downregulation of T-cell responses to A perfoliata. In vitro, A perfoliata excretory-secretory products induced apoptosis of the Jurkat T-cell line and premature cell death of ConA stimulated equine peripheral blood leucocytes. Analysis of cytokine transcription patterns in the leucocyte cultures showed a marked inhibition of IL-1 and IL-2 suggesting that a lack of T-cell growth factor transcription underlies the mechanism of the induced equine T-cell death. These preliminary findings suggest A perfoliata may have the ability to down-regulate host T-cell responses.
The profile of IL-4, IL-5, IL-10 and GATA3 in patients with LRBA deficiency and CVID with no known monogenic disease: Association with disease severity
ALLERGOLOGIA ET IMMUNOPATHOLOGIA
Authors: Azizi, G.; Bagheri, Y.; Yazdani, R.; Zaki-Dizaji, M.; Jamee, M.; Jadidi-Niaragh, F.; Kamali, A. N.; Abolhassani, H.; Aghamohammadi, A.
Abstract
Background: Common variable immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiency (PID). LPS-responsive beige-like anchor protein (LRBA) deficiency is an autosomal recessive disease characterized by a CVID-like phenotype. T cell abnormality was reported in patients with CVID and LRBA deficiency. The study's aim was to evaluate IL-4, IL-5, IL-10 and GATA3 expression in patients with LRBA deficiency and CVID with no known monogenic disease, and further evaluate its relevance with immunological futures and clinical complications of patients. Methods: The study population comprised patients with CVID, LRBA deficiency and age-sex matched healthy controls. Mutation analysis was done by whole exome sequencing in CVID patients to rule out monogenic PIDs. After CD4+ T cell stimulation with anti-CD3 and anti-CD28 monoclonal antibodies, gene expression of IL-4, IL-5, IL-10 and transcription factor GATA3 was evaluated by real-time polymerase chain reaction. The protein of mentioned cytokines was assessed by enzyme-linked immunosorbent assay. Results: The main clinical presentations of CVID patients were infections only and lymphoproliferations phenotypes, but in LRBA patients were autoimmune and enteropathy phenotype. The frequencies of CD4(+) T cells were significantly reduced in LRBA and CVID patients. There were no statistically significant differences among GATA3, IL4, and IL5 gene expressions by CD4(+). T cells of patients and controls, however, the IL10 expressions in CVID patients was significantly lower than in LRBA patients and HCs. As compared with HCs, CVID patients showed a prominent decrease in IL-4 and IL-10 production by CD4(+) T cells. Conclusions: Our findings demonstrated that patients with CVID and LRBA deficiency (even with severe infectious and inflammatory complications) have not imbalance in Th2 response, which is in parallel with lower frequency of allergy and asthma in these patients. (C) 2018 SEICAP. Published by Elsevier Espana, S.L.U. All rights reserved.