scholarly journals Contextual control of skin immunity and inflammation by Corynebacterium

2018 ◽  
Vol 215 (3) ◽  
pp. 785-799 ◽  
Author(s):  
Vanessa K. Ridaura ◽  
Nicolas Bouladoux ◽  
Jan Claesen ◽  
Y. Erin Chen ◽  
Allyson L. Byrd ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Envelope ◽  
Γδ T Cells ◽  
Mycolic Acid ◽  
Dependent Manner ◽  
Skin Microbiota ◽  
Skin Immune System ◽  
Dominant Component ◽  
Skin Immunity ◽  
The Impact

How defined microbes influence the skin immune system remains poorly understood. Here we demonstrate that Corynebacteria, dominant members of the skin microbiota, promote a dramatic increase in the number and activation of a defined subset of γδ T cells. This effect is long-lasting, occurs independently of other microbes, and is, in part, mediated by interleukin (IL)-23. Under steady-state conditions, the impact of Corynebacterium is discrete and noninflammatory. However, when applied to the skin of a host fed a high-fat diet, Corynebacterium accolens alone promotes inflammation in an IL-23–dependent manner. Such effect is highly conserved among species of Corynebacterium and dependent on the expression of a dominant component of the cell envelope, mycolic acid. Our data uncover a mode of communication between the immune system and a dominant genus of the skin microbiota and reveal that the functional impact of canonical skin microbial determinants is contextually controlled by the inflammatory and metabolic state of the host.

scholarly journals Skin Immune Landscape: Inside and Outside the Organism

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Florence Abdallah ◽  
Lily Mijouin ◽  
Chantal Pichon
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Skin Surface ◽  
Negative Influence ◽  
Background Information ◽  
Symbiotic Relationship ◽  
Skin Microbiota ◽  
Effector Cells ◽  
Skin Immune System ◽  
The Impact

The skin is an essential organ to the human body protecting it from external aggressions and pathogens. Over the years, the skin was proven to have a crucial immunological role, not only being a passive protective barrier but a network of effector cells and molecular mediators that constitute a highly sophisticated compound known as the “skin immune system” (SIS). Studies of skin immune sentinels provided essential insights of a complex and dynamic immunity, which was achieved through interaction between the external and internal cutaneous compartments. In fact, the skin surface is cohabited by microorganisms recognized as skin microbiota that live in complete harmony with the immune sentinels and contribute to the epithelial barrier reinforcement. However, under stress, the symbiotic relationship changes into a dysbiotic one resulting in skin disorders. Hence, the skin microbiota may have either positive or negative influence on the immune system. This review aims at providing basic background information on the cutaneous immune system from major cellular and molecular players and the impact of its microbiota on the well-coordinated immune responses in host defense.

Effect of plinabulin, a novel late-clinical stage immunotherapeutic agent on the adaptive and innate immune system.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 8-8
Author(s):  
Ramon W. Mohanlal ◽  
Lan Huang
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Clinical Stage ◽  
Onset Time ◽  
Immune Defense ◽  
Innate Immune ◽  
Dependent Manner ◽  
Breast Cancer Patients ◽  
Post Dose ◽  
The Impact

8 Background: Plinabulin (Plin) is a small molecule Dendritic Cell modulator, which in the presence of antigen, increases T-cell proliferation in an antigen-dependent manner marrow. The addition of Plin to Docetaxel (Doc) improved mOS with 4.6 months vs Docetaxel monotherapy, and prolonged DoR with more than 1 year (p < 0.05), which is indicative of an immune-mediated mechanism of action (Mohanlal, ASCO-SITC 2017). Neutrophils are our first line of innate immune defense against foreign invaders. We previously reported that Plinabulin prevents chemotherapy (Chemo) Induced Neutropenia (CIN) in patients receiving Doc or TAC throughout the cycle (Doc, Doxorubicin, Cyclophosphamide) (Blayney ASH 2018, St Gallen 2019). Here we analyzed the onset time of neutrophil increase following Plin administration. In addition, we analyzed the impact of Plin on plasma haptoglobin, which is an acute phase protein with anti-inflammatory effects together with immune-enhancing effects and is an integral part of innate immunity (Kristiansen Nature 2001). Methods: Absolute neutrophil count (ANC) and haptoglobin data were analyzed from Phase 2 study BPI-2358-106 (NCT03294577) with 10 (n = 15), 20 (n = 15) and 30 mg/m2 (n = 12) Plin in Breast Cancer patients receiving TAC. Plin was administered on Day 1. ANC and Haptoglobin were analyzed by a Central Laboratory (Covance), from blood draws at predose, and post-dose Plin at Day 2,3,6,7,8,9,10,11,12,13 and 15, and changes relative to predose value were evaluated. Results: Plin dose-dependently increased ANC within 1 day (P < 0.001) and Haptoglobin within 3 days (P < 0.03) of dosing. Mean haptoglobin (P < 0.0005) and ANC (P < 0.001) levels increased with ~two-fold vs baseline levels. ANC levels remained increased for approximately 1 week and haptoglobin levels for > 3 weeks. Conclusions: Based on Plinabulin’s ability to stimulate the innate system, together with its previously reported evidence as a potent activator of the adaptive immune system (Mohanlal, ASCO-SITC 2017), it is concluded that Plinabulin is a potent stimulator of the adaptive and innate immune system. Clinical trial information: NCT03294577.

scholarly journals Maternal Exposure Results in Long-Term Deoxynivalenol Persistence in Piglets’ Plasma and Modulates the Immune System

Toxins ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 615 ◽  
Author(s):  
Hana Štěpánová ◽  
Karolina Hlavová ◽  
Kamil Šťastný ◽  
Eduard Gopfert ◽  
Lenka Levá ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Γδ T Cells ◽  
High Sensitivity ◽  
Postnatal Period ◽  
Double Positive ◽  
Toxicological Effects ◽  
Immune Parameters ◽  
The Impact

Deoxynivalenol (DON)-contaminated feed represents a serious problem for pigs due to their high sensitivity to its toxicological effects. The aim of the present study was to evaluate the impact of intrauterine DON exposure on the immune system of piglets. Pure DON was intravenously administered to sows at the end of gestation (during the last 2–3 days of gestation, one dose of 300 µg per day). The plasma concentration of DON was analyzed using liquid chromatography combined with high-resolution Orbitrap-based mass spectrometry (LC–MS/MS (HR)) and selected immune parameters were monitored six times in piglets from birth to 18 weeks. DON was found in the plasma of 90% of newborn piglets at a mean concentration of 6.28 ng/mL and subsequently, at one, three, and seven weeks after birth with decreasing concentrations. Trace amounts were still present in the plasma 14 weeks after birth. Flow cytometry revealed a significant impact of DON on T lymphocyte subpopulations during the early postnatal period. Lower percentages of regulatory T cells, T helper lymphocytes, and their double positive CD4+CD8+ subset were followed by increased percentages of cytotoxic T lymphocytes and γδ T cells. The capacity to produce pro-inflammatory cytokines was also significantly lower after intrauterine DON exposure. In conclusion, this study revealed a long-term persistence of DON in the plasma of the piglets as a consequence of short-term intrauterine exposure, leading to altered immune parameters.

scholarly journals Secretion of proinflammatory cytokines by normal human melanocytes in response to lipopolysaccharide.

2011 ◽  
Vol 58 (4) ◽  
Author(s):  
Irena Tam ◽  
Krystyna Stępień
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Large Body ◽  
Dependent Manner ◽  
Skin Immune System ◽  
Human Melanocytes ◽  
Tnf Α ◽  
Normal Human ◽  
Dose Dependent

A large body of evidence suggests that epidermal melanocytes are an integral part of the skin immune system and can be considered immunocompetent cells. Recently, it has been reported that human melanocytes constitutively express Toll-like receptors and may be involved in the induction of several inflammatory cytokines. In the study the secretion of IL-1β, IL-6 and TNF-α by cultured normal melanocytes was investigated after stimulation with lipopolysaccharide. LPS increased the secretion of IL-1β in a dose-dependent manner. IL-1β stimulated release of IL-6 and TNF-α by melanocytes, whereas LPS activated production of TNF-α, but not of IL-6. These observations indicate that LPS can participate in the regulation of cytokine activity in normal human melanocytes and suggest that cytokines released by melanocytes could affect melanocytes themselves or/and other cells of the epidermis.

scholarly journals Mechanistic Analysis of Age-Related Clinical Manifestations in Down Syndrome

2021 ◽  
Vol 13 ◽  
Author(s):  
Xu-Qiao Chen ◽  
Zhuo Xing ◽  
Quang-Di Chen ◽  
Richard J. Salvi ◽  
Xuming Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Down Syndrome ◽  
Immune System ◽  
Clinical Manifestations ◽  
Chromosome 21 ◽  
Growth Delay ◽  
Biological Aging ◽  
Dependent Manner ◽  
Age Related ◽  
The Impact

Down syndrome (DS) is the most common genetic cause of Alzheimer’s disease (AD) due to trisomy for all or part of human chromosome 21 (Hsa21). It is also associated with other phenotypes including distinctive facial features, cardiac defects, growth delay, intellectual disability, immune system abnormalities, and hearing loss. All adults with DS demonstrate AD-like brain pathology, including amyloid plaques and neurofibrillary tangles, by age 40 and dementia typically by age 60. There is compelling evidence that increased APP gene dose is necessary for AD in DS, and the mechanism for this effect has begun to emerge, implicating the C-terminal APP fragment of 99 amino acid (β-CTF). The products of other triplicated genes on Hsa21 might act to modify the impact of APP triplication by altering the overall rate of biological aging. Another important age-related DS phenotype is hearing loss, and while its mechanism is unknown, we describe its characteristics here. Moreover, immune system abnormalities in DS, involving interferon pathway genes and aging, predispose to diverse infections and might modify the severity of COVID-19. All these considerations suggest human trisomy 21 impacts several diseases in an age-dependent manner. Thus, understanding the possible aging-related mechanisms associated with these clinical manifestations of DS will facilitate therapeutic interventions in mid-to-late adulthood, while at the same time shedding light on basic mechanisms of aging.

scholarly journals Maternal γδ T Cells Shape Offspring Pulmonary Type-2 Immunity In A Microbiota-Dependent Manner

2021 ◽  
Author(s):  
Pedro H. Papotto ◽  
Bahtiyar Yilmaz ◽  
Gonçalo Pimenta ◽  
Sofia Mensurado ◽  
Carolina Cunha ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Γδ T Cells ◽  
Female Reproductive Tract ◽  
Dependent Manner ◽  
Γδ T Cell ◽  
Type 2 Immunity ◽  
Immune System Development

Immune system development is greatly influenced by vertically transferred cues. However, beyond antibody-producing B cells, little is known about the role of other cell subsets of the maternal immune system in regulating offspring immunity. We reasoned γδ T cells to be attractive candidates based on their tissue distribution pattern: abundant in the skin, mammary glands and female reproductive tract. Here we found that mice born from γδ T cell-deficient (TCRδ-/-) dams display, early after birth, a pulmonary milieu selectively enriched in type-2 cytokines such as IL-33, IL-4, IL-5, and IL-13, and type-2-polarized immune cells, when compared to the progeny of γδ T cell-sufficient dams. In addition, upon helminth infection, mice born from TCRδ-/- dams sustained an increased type-2 inflammatory response. Critically, this was independent of the genotype of the pups. Despite similar levels of circulating antibodies in mothers and progeny, the intestinal microbiota in the offspring of TCRδ-/- and TCRδ+/- dams harbored distinct bacterial communities acquired during birth and fostering. These differences were accompanied by changes in the intestinal short-chain fatty acids (SCFA) profile. Importantly, antibiotic treatment abrogated the differences observed in the pulmonary milieu, and exogenous SCFA supplementation suppressed first-breath- and infection-induced inflammation. In summary, maternal γδ T cells control the establishment of a neonatal gut-lung axis by conditioning the postnatal microbial colonization of the offspring and bacterial-derived metabolite availability; ultimately impacting on the development of pulmonary type-2 immunity in the offspring.

scholarly journals Flux through lipid synthesis dictates bacterial cell size

2016 ◽  
Author(s):  
Stephen Vadia ◽  
Jessica L. Tse ◽  
Jue D. Wang ◽  
Petra Anne Levin
Keyword(s):  
Cell Size ◽  
Cell Envelope ◽  
Lipid Synthesis ◽  
Dependent Manner ◽  
Top Down ◽  
Cellular Integrity ◽  
Size And Morphology ◽  
Area Expansion ◽  
Open Question ◽  
The Impact

AbstractNutrients—and by extension biosynthetic capacity—positively impact cell size in organisms throughout the tree of life. In bacteria, cell size is reduced three-fold in response to nutrient starvation or accumulation of the alarmone ppGpp, a global inhibitor of biosynthesis. However, whether biosynthetic capacity as a whole determines cell size or if particular anabolic pathways are more important than others remains an open question. Utilizing a top-down approach, here we identify flux through lipid synthesis as the primary biosynthetic determinant ofEscherichia colicell size. Altering flux through lipid synthesis recapitulated the impact of altering nutrients on cell size and morphology, while defects in other biosynthetic pathways either did not impact size or altered size in a lipid-dependent manner. Together our findings support a model in which lipid availability dictates cell envelope capacity and ppGpp functions as a linchpin linking surface area expansion with cytoplasmic volume to maintain cellular integrity.

Aging and the skin immune system

1997 ◽  
Vol 133 (10) ◽  
pp. 1256-1262 ◽  
Author(s):  
C. Sunderkotter
Keyword(s):  
Immune System ◽  
Skin Immune System

Uncovering the Diversification of Tissue Engineering on the Emergent Areas of Stem Cells, Nanotechnology and Biomaterials

2020 ◽  
Vol 15 (3) ◽  
pp. 187-201 ◽  
Author(s):  
Sunil K. Dubey ◽  
Amit Alexander ◽  
Munnangi Sivaram ◽  
Mukta Agrawal ◽  
Gautam Singhvi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Immune System ◽  
Clinical Application ◽  
Cell Types ◽  
Patient Specific ◽  
Potential Strategy ◽  
Induced Pluripotent ◽  
Treat All ◽  
The Impact

Damaged or disabled tissue is life-threatening due to the lack of proper treatment. Many conventional transplantation methods like autograft, iso-graft and allograft are in existence for ages, but they are not sufficient to treat all types of tissue or organ damages. Stem cells, with their unique capabilities like self-renewal and differentiate into various cell types, can be a potential strategy for tissue regeneration. However, the challenges like reproducibility, uncontrolled propagation and differentiation, isolation of specific kinds of cell and tumorigenic nature made these stem cells away from clinical application. Today, various types of stem cells like embryonic, fetal or gestational tissue, mesenchymal and induced-pluripotent stem cells are under investigation for their clinical application. Tissue engineering helps in configuring the stem cells to develop into a desired viable tissue, to use them clinically as a substitute for the conventional method. The use of stem cell-derived Extracellular Vesicles (EVs) is being studied to replace the stem cells, which decreases the immunological complications associated with the direct administration of stem cells. Tissue engineering also investigates various biomaterials to use clinically, either to replace the bones or as a scaffold to support the growth of stemcells/ tissue. Depending upon the need, there are various biomaterials like bio-ceramics, natural and synthetic biodegradable polymers to support replacement or regeneration of tissue. Like the other fields of science, tissue engineering is also incorporating the nanotechnology to develop nano-scaffolds to provide and support the growth of stem cells with an environment mimicking the Extracellular matrix (ECM) of the desired tissue. Tissue engineering is also used in the modulation of the immune system by using patient-specific Mesenchymal Stem Cells (MSCs) and by modifying the physical features of scaffolds that may provoke the immune system. This review describes the use of various stem cells, biomaterials and the impact of nanotechnology in regenerative medicine.

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