Allergen-Specific Immunotherapy With Liposome Containing CpG-ODN in Murine Model of Asthma Relies on MyD88 Signaling in Dendritic Cells
FRONTIERS IN IMMUNOLOGY
Authors: Alberca-Custodio, Ricardo Wesley; Faustino, Lucas D.; Gomes, Eliane; Nunes, Fernanda Peixoto Barbosa; de Siqueira, Mirian Krystel; Labrada, Alexis; Almeida, Rafael Ribeiro; Camara, Niels Olsen Saraiva; da Fonseca, Denise Morais; Russo, Momtchilo
Abstract
Changing the immune responses to allergens is the cornerstone of allergen immunotherapy. Allergen-specific immunotherapy that consists of repeated administration of increasing doses of allergen extract is potentially curative. The major inconveniences of allergen-specific immunotherapy include failure to modify immune responses, long-term treatment leading to non-compliance and the potential for developing life-threating anaphylaxis. Here we investigated the effect of a novel liposomal formulation carrying low dose of allergen combined with CpG-ODN, a synthetic TLR9 agonist, on established allergic lung inflammation. We found that challenge with allergen (OVA) encapsulated in cationic liposome induced significantly less severe cutaneous anaphylactic reaction. Notably, short-term treatment (three doses) with a liposomal formulation containing co-encapsulated allergen plus CpG-ODN, but not allergen or CpG-ODN alone, reversed an established allergic lung inflammation and provided long-term protection. This liposomal formulation was also effective against allergens derived from Blomia tropicalis mite extract. The attenuation of allergic inflammation was not associated with increased numbers of Foxp3-positive or IL-10-producing regulatory T cells or with increased levels of IFN-gamma in the lungs. Instead, the anti-allergic effect of the liposomal formulation was dependent of the innate immune signal transduction generated in CD11c-positive putative dendritic cells expressing MyD88 molecule. Therefore, we highlight the pivotal role of dendritic cells in mediating the attenuation of established allergic lung inflammation following immunotherapy with a liposomal formulation containing allergen plus CpG-ODN.
Interrelationships of vitelline and muscle cells within the vitelline follicles of the blood fluke Aporocotyle simplex (Digenea, Aporocotylidae) and morphological evidence for the modification of vitelline material for eggshell formation
PARASITOLOGY RESEARCH
Authors: Poddubnaya, Larisa G.; Hemmingsen, Willy; Brunanska, Magdalena; Gibson, David, I
Abstract
This study of the fish blood flukeAporocotyle simplexrepresents the first detailed transmission electron microscopical (TEM) investigation of the vitellarium of an aporocotylid digenean blood fluke. It revealed some unusual characteristics in the cytoarchitecture of the vitelline follicles and demonstrated modifications of the vitelline granules for eggshell formation. The vitelline follicles consist of vitellocytes at different developmental stages surrounded by sarcoplasmic processes of myocytes which occur throughout each follicle. Sites of intimate contact occur between the vitellocytes and the myocytes. Individual vitelline globules (0.1-0.2 mu m in diameter) accumulate in quite small clusters of 10-20 and have a dense, heterogeneous matrix possessing central and peripheral regions with a greater density. Modifications of the vitelline globules take place within the clusters and are first apparent when the vitellocytes reach the lumen of the vitelline duct and vitelline reservoir. Globules within the clusters become confluent, and, when the vitellocytes reach the lumen of the oviduct and proximal ootype, these consolidated clusters contain a shapeless, loosely packed, dense material which is released from the vitellocytes by exocytosis. This investigation has provided morphological evidence for shell formation from modified vitelline globules in the form of a discontinuous, thin layer (similar to 0.07 mu m in thickness) of electron-dense shell material around the fertilized ovum and associated vitellocytes in the proximal ootype. The eggshell of intra-uterine eggs acquires an additional thin, heterogeneous outer layer, increasing its thickness to similar to 0.1 mu m. The cytoarchitecture of the vitellarium, modifications of the vitelline globules within the clusters and the structure of the eggshell ofA. simplexmay prove to be of value in studies examining relationships between the three distinct lineages of aporocotylid digeneans.