Abstract:Psoriasis (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are common diseases dependent on environmental factors that activate the immune system in unknown ways. Mannan is a group of polysaccharides common in the environment; they are potentially pathogenic, because at least some of them induce Ps-, PsA-and RA-like inflammation in mice. Here, we used positron emission tomography/computed tomography to examine in-vivo transport and spread of mannan labelled with fluorine-18 [ 18 F]. The results sh… Show more
“…3 C) in peri-entheseal bone marrow but not in entheseal soft tissue (data not shown). It has previously been shown in mice that intraperitoneal fungal adjuvants rapidly spread to the joints and tibial bone marrow [ 41 ]. Fig.…”
Background
Neutrophils are present in the early phases of spondyloarthritis-related uveitis, skin and intestinal disease, but their role in enthesitis, a cardinal musculoskeletal lesion in spondyloarthritis, remains unknown. We considered the role of neutrophils in the experimental SKG mouse model of SpA and in human axial entheses.
Methods
Early inflammatory infiltrates in the axial and peripheral entheseal sites in SKG mice were evaluated using immunohistochemistry and laser capture microdissection of entheseal tissue. Whole transcriptome analysis was carried out using Affymetrix gene array MTA 1.0, and data was analyzed via IPA. We further isolated neutrophils from human peri-entheseal bone and fibroblasts from entheseal soft tissue obtained from the axial skeleton of healthy patients and determined the response of these cells to fungal adjuvant.
Results
Following fungal adjuvant administration, early axial and peripheral inflammation in SKG mice was characterized by prominent neutrophilic entheseal inflammation. Expression of transcripts arising from neutrophils include abundant mRNA for the alarmins S100A8 and S100A9. In normal human axial entheses, neutrophils were present in the peri-entheseal bone. Upon fungal stimulation in vitro, human neutrophils produced IL-23 protein, while isolated human entheseal fibroblasts produced chemokines, including IL-8, important in the recruitment of neutrophils.
Conclusion
Neutrophils with inducible IL-23 production are present in uninflamed human entheseal sites, and neutrophils are prominent in early murine spondyloarthritis-related enthesitis. We propose a role for neutrophils in the early development of enthesitis.
“…3 C) in peri-entheseal bone marrow but not in entheseal soft tissue (data not shown). It has previously been shown in mice that intraperitoneal fungal adjuvants rapidly spread to the joints and tibial bone marrow [ 41 ]. Fig.…”
Background
Neutrophils are present in the early phases of spondyloarthritis-related uveitis, skin and intestinal disease, but their role in enthesitis, a cardinal musculoskeletal lesion in spondyloarthritis, remains unknown. We considered the role of neutrophils in the experimental SKG mouse model of SpA and in human axial entheses.
Methods
Early inflammatory infiltrates in the axial and peripheral entheseal sites in SKG mice were evaluated using immunohistochemistry and laser capture microdissection of entheseal tissue. Whole transcriptome analysis was carried out using Affymetrix gene array MTA 1.0, and data was analyzed via IPA. We further isolated neutrophils from human peri-entheseal bone and fibroblasts from entheseal soft tissue obtained from the axial skeleton of healthy patients and determined the response of these cells to fungal adjuvant.
Results
Following fungal adjuvant administration, early axial and peripheral inflammation in SKG mice was characterized by prominent neutrophilic entheseal inflammation. Expression of transcripts arising from neutrophils include abundant mRNA for the alarmins S100A8 and S100A9. In normal human axial entheses, neutrophils were present in the peri-entheseal bone. Upon fungal stimulation in vitro, human neutrophils produced IL-23 protein, while isolated human entheseal fibroblasts produced chemokines, including IL-8, important in the recruitment of neutrophils.
Conclusion
Neutrophils with inducible IL-23 production are present in uninflamed human entheseal sites, and neutrophils are prominent in early murine spondyloarthritis-related enthesitis. We propose a role for neutrophils in the early development of enthesitis.
“… 83 , 84 “Mannan degradation” involves mannan oligosaccharides, which broadly activate the immune system including complement and neutrophils, two central components in arthritis pathogenesis. 85 Bacterial-derived “Arginine deiminase” has anti-inflammatory properties, reducing LPS-induced responses 86 and colitis in mice. 87 “Propionate catabolism” is another important metagenome pathway that was abundant in the Mg2800 group, and implicated in SCFA.…”
“…Over the past two decades, there have been numerous studies investigating the use of yeasts in raising an immune response against different pathogenic species (58-60). While certain pathogenic yeasts have developed immuneevading strategies, such as epitope-masking to control the production and exposure of highly antigenic cell wall proteins (Candida albicans) (58) or epigenetic switching to selectively silence their expression (Plasmodium species, Pneumocystis species, and Trypanosoma) (59), the high cell wall antigenicity other yeast such Saccharomyces cerevisiae make them prime candidates for the creation of vaccine adjuvants (60). The yeast cell wall compiles multiple highly antigenic components in a single location enabling a multi-pronged immune activation, namely through the recognition of β-glucans by dectin-1 and CR3 leading to activation of other inflammatory cells and T-cell responses (58,59,61).…”
Section: The Impact Of Yeasts On the Immune Systemmentioning
confidence: 99%
“…Because most yeasts trigger a rapid immune response, disease applications where treatment efficacy and immune stimulation can function synergistically are preferred (58)(59)(60). Due to the low transfection efficiency, it is generally advised to restrict yeast-encapsulated gene-editing therapies to the GI tract alone (24,47,66).…”
Section: Disease Targets For Oral Yeast Systemsmentioning
Oral vaccine and gene delivery systems must be engineered to withstand several different physiological environments, such as those present in the oral cavity, stomach, and jejunum, each of which exhibits varying pH levels and enzyme distributions. Additionally, these systems must be designed to ensure appropriate gastrointestinal absorption and tissue/cellular targeting properties. Although a plethora of nanomaterials are employed in the construction of these delivery devices, yeasts display unique characteristics, such a rigid cell wall and a resistance to harsh environments, that make them a prime vehicle for oral delivery of active pharmaceutical agents, vaccines, and genetic material. The ability of yeast cells to adhere to other cells or substrates is a crucial property that allows for more efficient gastrointestinal passage and subsequent systemic circulation, which has enabled substantial advancements in therapeutic efficacy in the pharmaceutical arena. Among several discoveries, the feasibility of yeast for vaccine and gene delivery is supported by findings from recent studies that yeasts have the ability to independently activate or deactivate separate but co-functioning portions of the immune system to synergistically ameliorate treatment effects. The purpose of this review is to present current information on the uses of yeast in the development of oral vaccines and gene delivery systems with an emphasis on yeast-related mechanisms of immune system activation, along with potential clinical implications in terms of disease targets and approaches to formulations.
ResultsThe oral route for delivery of vaccines and gene therapies offers a number of advantages, including ease of administration, manufacturing efficiency, and cost. However, before widespread adoption of this therapeutic modality can occur, factors such as adequate local and systemic availability of the therapeutic agent and accurate targeting of tissues and cells, are just some of the challenges that must be addressed. Yeasts-based delivery vehicles are excellent candidates for oral vaccine and oral gene therapies as many species possess cellular characteristics resulting in enhanced resistance to the harsh gastrointestinal (GI) environment and facilitated passage across the mucosal barrier. Yeast capsules can stimulate and modulate host immune responses, which is beneficial for vaccine efficacy. In addition, recombinant modification of yeasts to express cell penetrating proteins and injection mechanisms along with efficient cell adhering capabilities can potentially improve transfection rates of genetic material. In this literature review, we present evidence supporting the beneficial role yeast-based delivery systems can play in increasing the efficacy of oral administration of vaccines and gene therapies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
