scholarly journals Interactions of host defense and hyper-keratinization in psoriasis

2021 ◽  
Author(s):  
Jingwen Deng ◽  
Emmerik Leijten ◽  
Michel Olde Nordkamp ◽  
Hartgring Sarita ◽  
Weiyang Tao ◽  
...  

Objectives: To understand the crosstalk between the host and microbiota in psoriatic skin, using a systems biology approach based on transcriptomics and microbiome profiling. Methods: We collected the skin tissue biopsies and swabs in both lesion and non-lesion skin of 13 patients with psoriasis (PsO), 15 patients with psoriatic arthritis (PsA), and healthy skin from 12 patients with ankylosing spondylitis (AS). We performed transcriptome sequencing and metagenomics profiling on the local skin sites to study the similarities and differences in the molecular profiles between the three conditions, and the associations between the host defense and microbiota dynamic. Results: We found that lesion and non-lesional samples were remarkably different in terms of their transcriptome profiles. Functional annotation of differentially expressed genes (DEGs) showed a major enrichment in neutrophil activation. By using co-expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we extracted a "core" set of genes that were functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundance of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the "core network" of genes. Conclusions: We identified a core network that regulates inflammation and hyper-keratinization in psoriatic skin, and is associated with local disease severity and microbiome composition.

2017 ◽  
Vol 1 (S1) ◽  
pp. 15-15
Author(s):  
Di Yan ◽  
Hsin-Wen Chang ◽  
Rasnik Singh ◽  
Kevin Lai ◽  
Kristina Lee ◽  
...  

OBJECTIVES/SPECIFIC AIMS: Psoriasis is one of the most common inflammatory diseases of the skin, affecting about 2%–3% of the US population. Despite its high prevalence, its pathogenesis remains poorly understood. The ability of the microbiome to modify host immunity and metabolism suggests that it may contribute to the development of psoriasis and its cardiometabolic comorbidities. This study aims to characterize the psoriatic skin microbiome and understand the functional role that these bacteria may play. METHODS/STUDY POPULATION: 16s rRNA sequencing of site-matched skin swabs from 8 psoriasis patients and 8 healthy controls was used to identify bacteria and determine their relative abundance and microbial community diversity in the sample. PICRUSt was used to infer the functional roles of the bacteria from 16s rRNA amplicon data. RESULTS/ANTICIPATED RESULTS: Lesional psoriasis skin had lower α diversity (p=0.04), less Actinobacteria (p=0.0001), but higher Firmicutes (p=0.009) compared with controls. At the genus level, lesional skin had more Alloiococcus (p=0.01) and Aerococcus (p=0.01) and demonstrated a trend towards lower Propionibacterium (p=0.08) and higher Gallicola (p=0.09) compared to controls. Interestingly, Alloiococcus (p=0.003) and Gallicola (p=0.04) were also higher in nonlesional skin compared with controls. Furthermore, lesional and nonlesional skin shared an increased abundance of Acinetobacter sp., Staphylococcus pettenkoferi, and Streptococcus sp., relative to controls. Lesional and nonlesional psoriasis skin did not differ significantly in microbiome composition. Predictive functional analysis revealed that both the healthy and psoriatic skin microbiome were enriched with bacteria capable of amino acid and carbohydrate metabolism suggest these functions might have a general role in host-microbe interaction. DISCUSSION/SIGNIFICANCE OF IMPACT: These data reveal intriguing differences in the cutaneous microbiome of psoriatic individuals and healthy controls and suggest that bacterial metabolism may play an important role in host-microbe interaction.


2017 ◽  
Vol 284 (1857) ◽  
pp. 20170944 ◽  
Author(s):  
Andrea J. Jani ◽  
Roland A. Knapp ◽  
Cheryl J. Briggs

Infectious diseases have serious impacts on human and wildlife populations, but the effects of a disease can vary, even among individuals or populations of the same host species. Identifying the reasons for this variation is key to understanding disease dynamics and mitigating infectious disease impacts, but disentangling cause and correlation during natural outbreaks is extremely challenging. This study aims to understand associations between symbiotic bacterial communities and an infectious disease, and examines multiple host populations before or after pathogen invasion to infer likely causal links. The results show that symbiotic bacteria are linked to fundamentally different outcomes of pathogen infection: host–pathogen coexistence (endemic infection) or host population extirpation (epidemic infection). Diversity and composition of skin-associated bacteria differed between populations of the frog, Rana sierrae , that coexist with or were extirpated by the fungal pathogen, Batrachochytrium dendrobatidis (Bd). Data from multiple populations sampled before or after pathogen invasion were used to infer cause and effect in the relationship between the fungal pathogen and symbiotic bacteria. Among host populations, variation in the composition of the skin microbiome was most strongly predicted by pathogen infection severity, even in analyses where the outcome of infection did not vary. This result suggests that pathogen infection shapes variation in the skin microbiome across host populations that coexist with or are driven to extirpation by the pathogen. By contrast, microbiome richness was largely unaffected by pathogen infection intensity, but was strongly predicted by geographical region of the host population, indicating the importance of environmental or host genetic factors in shaping microbiome richness. Thus, while both richness and composition of the microbiome differed between endemic and epidemic host populations, the underlying causes are most likely different: pathogen infection appears to shape microbiome composition, while microbiome richness was less sensitive to pathogen-induced disturbance. Because higher richness was correlated with host persistence in the presence of Bd, and richness appeared relatively stable to Bd infection, microbiome richness may contribute to disease resistance, although the latter remains to be directly tested.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3220-3220
Author(s):  
Norah Verbout ◽  
Asako Itakura ◽  
Joseph Aslan ◽  
Erik Tucker ◽  
Andras Gruber ◽  
...  

Abstract Abstract 3220 Neutrophils play a vital role in innate immunity. Activated neutrophils can release proteolytic enzymes capable of neutralizing microbes and contributing importantly to host-defense. In severe sepsis, microbial components and pro-inflammatory cytokines can contribute to excess systemic neutrophil activation, resulting in tissue damage and organ failure. Thus, regulation of neutrophil activation and factor release is critical during pathologic conditions. Recent data indicate that components of the contact system modulate numerous inflammatory mediators during severe sepsis, but the exact role of the contact pathway in host-defense is not well understood. Inhibition of factor XII (FXII) in septic baboons reduces circulating neutrophil elastase (NE), a potent cytolytic enzyme that is increased during sepsis and implicated in organ failure. In vitro studies also indicate that both plasma kallikrein and FXIIa are capable of directly inducing NE release. While it is apparent that factors of the contact system interact with neutrophils, the molecular mechanisms by which these factors modulate neutrophil function have not been established. We therefore examined factor XI (FXI) neutrophil interactions and the cellular signaling pathways regulating FXIIa neutrophil stimulation. Human neutrophils were isolated from peripheral blood and resuspended in HBSS at a concentration of 0.5 ×106/ml. Cells were treated with FXI, FXIa, FXII, or FXIIa with or without fMLP (1 μM) stimulation, and the release of NE was assayed in the cell supernatants via ELISA. FXI, FXIa or FXII had no direct stimulatory effect on NE release compared to vehicle. While neither FXI nor FXII had any inhibitory effect on fMLP induced NE release, FXIa (10 μg/ml) modestly reduced fMLP-induced NE release by 20% (n=3). FXIIa (3, 10, 30 μg/ml) dose-dependently increased NE release in the presence of cytochalasin B (5 μg/ml), consistent with published data. To examine the mechanism by which FXIIa induces NE release, neutrophils were pretreated with signaling inhibitors and subsequently activated with FXIIa (30 μg/ml). Mammalian target of rapamycyin (mTOR) is a downstream serine/threonine kinase of the PI3K/AKT pathway that integrates signals from the microenvironment such as cytokines and growth factors. It is known that inhibition of mTORC2 abrogates neutrophil polarization and directed migration, thus we examined the role of rapamycin complex 1 and 2 (mTORC1/2) in mediating NE release. Pretreatment of cells with RAD001 (20 nM), an mTORC1 inhibitor had no effect on FXIIa-induced NE release, whereas the combined mTORC1/mTORC2 inhibitor, pp242 (100 nM) abrogated FXIIa-induced NE release, suggesting that components of the mTORC2 pathway contribute to NE release. Pretreatment with EHT 1864 (50 uM), a Rac inhibitor, significantly potentiated NE release induced by either fMLP or FXIIa, suggesting that Rac is also capable of modulating FXIIa signaling. Taken together, these results suggest that coagulation factors FXIa and FXIIa differentially modulate neutrophil function, and that the mTOR and Rac signaling pathways participate in FXIIa stimulated neutrophil activation. These data suggest that the contact pathway is involved in neutrophil stimulation through mTOR and Rac signaling, and thus modulating these pathways could be a potential therapeutic strategy for limiting excess neutrophil activation. Disclosures: Gruber: Aronora, LLC: Consultancy, Equity Ownership.


2017 ◽  
Vol 137 (5) ◽  
pp. S102
Author(s):  
H. Ahmed ◽  
C. Morrow ◽  
N. Yusuf ◽  
H.W. Lim ◽  
I. Hamzavi ◽  
...  

2021 ◽  
Author(s):  
Fardou H. Heida ◽  
Elisabeth M. W. Kooi ◽  
Josef Wagner ◽  
Thi-Yen Nguyen ◽  
Jan B. F. Hulscher ◽  
...  

Abstract Background: The intestinal microbiome in preterm infants differs markedly from term infants. It is unclear whether the microbiome develops over time according to infant specific factors. Methods: We analysed (clinical) metadata - to identify the main factors influencing the microbiome composition development - and the first meconium and feacal samples til the 4th week via 16S rRNA amplican sequencing. Results: We included 41 infants (gestational age 25-30 weeks; birth weight 430-990g. Birth via Caesarean section (CS) was associated with placental insufficiency during pregnancy and lower BW. In meconium and in weeks 2 and 3 an increased combined abundance of Escherichia and Bacteroides (maternal fecal representatives) was associated with vaginal delivery (p=0.021, p=0.0002, p=0.028, respectively) while Staphylococcus (skin microbiome representative) was associated with CS (p=0.0008, p=0.0003 p=0.046, respectively). Secondly, irrespective of the week of sampling or the mode of birth, a transition was observed as children children gradually increased in weight from a microbiome dominated by Staphylococcus (Bacilli) towards a microbiome dominated by Enterobacteriaceae (Gammaproteobacteria). Conclusions: Mode of delivery affects the meconium microbiome composition. It also suggests that the weight of the infant at the time of sampling is a better predictor for the stage of progression of the intestinal microbiome development/maturation than postconceptional age.


2019 ◽  
Author(s):  
C Pepe-Ranney ◽  
C Keyser ◽  
J Trimble ◽  
B Bissinger

AbstractFarmers grow sweetpotatoes worldwide and some sub-Saharan African and Asian diets include sweetpotato as a staple, yet the sweetpotato microbiome is conspicuously less studied relative to crops such as maize, soybean, and wheat. Studying sweetpotato microbiome ecology may reveal paths to engineer the microbiome to improve sweetpotato yield, and/or combat sweetpotato pests and diseases. We sampled sweetpotatoes and surrounding soil from two North Carolina farms. We took samples from sweetpotato fields under two different land management regimes, conventional and organic, and collected two sweetpotato cultivars, ‘Beauregard’ and ‘Covington’. By comparing SSU rRNA gene amplicon sequence profiles from sweetpotato storage root skin, rhizosphere, and surrounding soil we found the skin microbiome possessed the least composition heterogeneity among samples and lowest alpha-diversity and was significantly nested by the rhizosphere in amplicon sequence variant (ASV) membership. Many ASVs were specific to a single field and/or only found in either the skin, rhizosphere, or surrounding soil. Notably, sweetpotato skin enriched for Planctomycetaceae in relative abundance at both farms. This study elucidates underpinnings of sweetpotato microbiome community assembly, quantifies microbiome composition variance within a single farm, and reveals microorganisms associated with sweetpotato skin that belong to common but uncultured soil phylotypes.


2019 ◽  
Author(s):  
Roo Vandegrift ◽  
Ashkaan K. Fahimipour ◽  
Mario Muscarella ◽  
Ashley C. Bateman ◽  
Kevin Van Den Wymelenberg ◽  
...  

AbstractThe human skin microbiome interacts intimately with human health, yet the drivers of skin microbiome composition and diversity are not well-understood. The composition of the skin microbiome has been characterized as both highly variable and relatively stable, depending on the time scale under consideration, and it is not clear what role contact with environmental sources of microbes plays in this variability. We experimentally mimicked human skin contact with two common environmental sources of microorganisms — soils and plant leaves — and characterized the dynamics of microbial acquisition and persistence on skin on very short time scales. Repeatable changes in skin community composition following encounters with environmental sources were observed, and these trajectories largely depend on donor community biomass distributions. Changes in composition persisted for at least 24 hours and through a soap and water wash following exposures to relatively high biomass soil communities. In contrast, exposures to lower biomass leaf communities were undetectable after a 24 hour period. Absolute abundances of bacterial taxa in source communities predicted transmission probabilities and residence times, independent of phylogenetic considerations. Our results suggest that variability in the composition of the skin microbiome can be driven by transient encounters with common environmental sources, and that these relatively transient effects can persist when the source is of sufficient biomass.ImportanceHumans come into contact with environmental sources of microbes, such as soil or plants, constantly. Those microbial exposures have been linked to health through training and modulation of the immune system. While much is known about the human skin microbiome, the short term dynamics after a contact event, such as touching soil, have not been well characterized. In this study, we examine what happens after such a contact event, describing trends in microbial transmission to and persistence on the skin. Additionally, we use computational sampling model simulations to interrogate null expectations for these kinds of experiments. This work has broad implications for infection control strategies and therapeutic techniques that rely on modification of the microbiome, such as probiotics and faecal transplantation.


2021 ◽  
Vol 9 (2) ◽  
pp. 353
Author(s):  
Britta De Pessemier ◽  
Lynda Grine ◽  
Melanie Debaere ◽  
Aglaya Maes ◽  
Bernhard Paetzold ◽  
...  

The microbiome plays an important role in a wide variety of skin disorders. Not only is the skin microbiome altered, but also surprisingly many skin diseases are accompanied by an altered gut microbiome. The microbiome is a key regulator for the immune system, as it aims to maintain homeostasis by communicating with tissues and organs in a bidirectional manner. Hence, dysbiosis in the skin and/or gut microbiome is associated with an altered immune response, promoting the development of skin diseases, such as atopic dermatitis, psoriasis, acne vulgaris, dandruff, and even skin cancer. Here, we focus on the associations between the microbiome, diet, metabolites, and immune responses in skin pathologies. This review describes an exhaustive list of common skin conditions with associated dysbiosis in the skin microbiome as well as the current body of evidence on gut microbiome dysbiosis, dietary links, and their interplay with skin conditions. An enhanced understanding of the local skin and gut microbiome including the underlying mechanisms is necessary to shed light on the microbial involvement in human skin diseases and to develop new therapeutic approaches.


2021 ◽  
Vol 141 (5) ◽  
pp. S39
Author(s):  
Z.T. Nolan ◽  
K. Banerjee ◽  
Z. Cong ◽  
S. Gettle ◽  
A. Longenecker ◽  
...  

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