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1.
Nat Commun ; 12(1): 5967, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645809

RESUMO

The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.


Assuntos
Colo do Útero/metabolismo , Imunidade Inata , Metaboloma/imunologia , Microbiota/imunologia , Nascimento Prematuro/metabolismo , Vagina/metabolismo , Adulto , Cerclagem Cervical/métodos , Colo do Útero/imunologia , Colo do Útero/microbiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/imunologia , Nascimento Prematuro/microbiologia , Estudos Prospectivos , Espectrometria de Massas por Ionização por Electrospray , Vagina/imunologia , Vagina/microbiologia
2.
Cells ; 10(9)2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34571999

RESUMO

Like all invertebrates, flies such as Drosophila lack an adaptive immune system and depend on their innate immune system to protect them against pathogenic microorganisms and parasites. In recent years, it appears that the nervous systems of eucaryotes not only control animal behavior but also cooperate and synergize very strongly with the animals' immune systems to detect and fight potential pathogenic threats, and allow them to adapt their behavior to the presence of microorganisms and parasites that coexist with them. This review puts into perspective the latest progress made using the Drosophila model system, in this field of research, which remains in its infancy.


Assuntos
Drosophila/imunologia , Microbiota/imunologia , Neurônios/imunologia , Parasitos/imunologia , Imunidade Adaptativa/imunologia , Animais , Drosophila/microbiologia , Drosophila/parasitologia , Interações Hospedeiro-Parasita/imunologia , Imunidade Inata/imunologia , Neurônios/microbiologia , Neurônios/parasitologia
3.
Front Immunol ; 12: 680845, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484179

RESUMO

The current coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has resulted in a major global pandemic, causing extreme morbidity and mortality. Few studies appear to suggest a significant impact of gender in morbidity and mortality, where men are reported at a higher risk than women. The infectivity, transmissibility, and varying degree of disease manifestation (mild, modest, and severe) in population studies reinforce the importance of a number of genetic and epigenetic factors, in the context of immune response and gender. The present review dwells on several contributing factors such as a stronger innate immune response, estrogen, angiotensin-converting enzyme 2 gene, and microbiota, which impart greater resistance to the SARS-CoV-2 infection and disease progression in women. In addition, the underlying importance of associated microbiota and certain environmental factors in gender-based disparity pertaining to the mortality and morbidity due to COVID-19 in women has also been addressed.


Assuntos
COVID-19/imunologia , Hormônios Esteroides Gonadais , Disparidades em Assistência à Saúde , Imunidade Inata , SARS-CoV-2/imunologia , COVID-19/epidemiologia , COVID-19/mortalidade , Progressão da Doença , Feminino , Saúde Global , Humanos , Masculino , Microbiota/imunologia , Fatores de Risco , Fatores Sexuais
4.
Nat Immunol ; 22(11): 1428-1439, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34471264

RESUMO

Coordinated local mucosal and systemic immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either protect against coronavirus disease 2019 (COVID-19) pathologies or fail, leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct patients with COVID-19 during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. By contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microorganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.


Assuntos
COVID-19/imunologia , Microbiota/imunologia , Nasofaringe/imunologia , SARS-CoV-2/fisiologia , Doença Aguda , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Estudos de Coortes , Feminino , Humanos , Imunidade Humoral , Imunidade nas Mucosas , Interferons/sangue , Masculino , Pessoa de Meia-Idade , Nasofaringe/microbiologia , Glicoproteína da Espícula de Coronavírus/imunologia , Carga Viral , Adulto Jovem
5.
J Immunol ; 207(8): 1959-1963, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34544802

RESUMO

Previous studies indicate that IL-17A plays an important role in mediating the intestinal microbiota and systemic metabolic functions. However, it is not known where IL-17RA signaling occurs to mediate these effects. To investigate this question, we used intestinal epithelial-specific (Il17ra ΔIEC ) and liver-specific (Il17raΔLiver ) IL-17RA knockout mice as well as littermate control mice. Our results indicate that intestinal IL-17RA signaling helps mediate systemic metabolic functions upon exposure to prolonged high-fat diet. Il17ra ΔIEC mice display impaired glucose metabolism, altered hormone and adipokine levels, increased visceral adiposity, and greater hepatic lipid deposition when compared with their littermate controls. We show that IL-17RA-driven changes in microbiota composition are responsible for regulating systemic glucose metabolism. Altogether, our data elucidate the importance of intestinal IL-17RA signaling in regulating high-fat diet-mediated systemic glucose and lipid metabolism.


Assuntos
Interleucina-17/metabolismo , Mucosa Intestinal/fisiologia , Fígado/fisiologia , Doenças Metabólicas/imunologia , Microbiota/imunologia , Receptores de Interleucina-17/metabolismo , Adipocinas/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Glucose/metabolismo , Hormônios/metabolismo , Humanos , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais
7.
J Immunol ; 207(7): 1719-1724, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544814

RESUMO

Metabolic diseases are common worldwide and include diseases of overnutrition, such as obesity, or undernutrition, such as kwashiorkor. Both the immune system and the microbiota contribute to a variety of metabolic diseases; however, these two processes have largely been studied independently of one another in this context. The gastrointestinal system houses the greatest density of microbes but also houses one of the largest collections of immune molecules, especially Abs. The IgA isotype dominates the Ab landscape at mucosal sites, and a number of studies have demonstrated the importance of this Ab to the stability of the microbiota. In this article, we review the literature that demonstrates how homeostatic Ab responses control microbiota composition and function to influence metabolic disease. We propose that many metabolic diseases may arise from disruptions to homeostatic immune control of gut commensals and that further understanding this interaction can offer a novel opportunity for therapeutic interventions.


Assuntos
Disbiose/imunologia , Imunoglobulina A/metabolismo , Doenças Metabólicas/imunologia , Microbiota/imunologia , Membrana Mucosa/imunologia , Animais , Disbiose/microbiologia , Interações entre Hospedeiro e Microrganismos , Humanos , Imunidade nas Mucosas , Imunomodulação , Doenças Metabólicas/microbiologia , Membrana Mucosa/microbiologia
8.
J Immunol ; 207(7): 1710-1718, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544813

RESUMO

The microbiota-the diverse set of commensal microbes that normally colonize humans-represents the first line of defense against infectious diseases. In this review, we summarize the direct and indirect mechanisms by which the microbiota modulates susceptibility to, and severity of, infections, with a focus on immunological mechanisms. Moreover, we highlight some of the ways that modern-world lifestyles have influenced the structure-function relationship between the microbiota and infectious diseases. Ultimately, understanding how the microbiota influences infectious risks will facilitate development of microbiota-derived therapeutics that bolster host defenses.


Assuntos
Infecções/imunologia , Microbiota/imunologia , Animais , Terapia Biológica , Suscetibilidade a Doenças , Interações entre Hospedeiro e Microrganismos , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Infecções/microbiologia , Relação Estrutura-Atividade
9.
J Immunol ; 207(7): 1725-1733, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544815

RESUMO

The trillions of bacteria that constitutively colonize the human gut collectively generate thousands of unique small molecules. These microbial metabolites can accumulate both locally and systemically and potentially influence nearly all aspects of mammalian biology, including immunity, metabolism, and even mood and behavior. In this review, we briefly summarize recent work identifying bioactive microbiota metabolites, the means through which they are synthesized, and their effects on host physiology. Rather than offering an exhaustive list of all known bioactive microbial small molecules, we select a few examples from each key class of metabolites to illustrate the diverse impacts of microbiota-derived compounds on the host. In addition, we attempt to address the microbial logic behind specific biotransformations. Finally, we outline current and emerging strategies for identifying previously undiscovered bioactive microbiota metabolites that may shape human health and disease.


Assuntos
Microbiota/imunologia , Aminoácidos/metabolismo , Animais , Aminas Biogênicas/metabolismo , Fibras na Dieta/metabolismo , Ácidos Graxos Voláteis/metabolismo , Interações entre Hospedeiro e Microrganismos , Humanos , Metilaminas/metabolismo
10.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188626, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34520804

RESUMO

The human body harbors a vast array of microbiota that modulates host pathophysiological processes and modifies the risk of diseases including cancer. With the advent of metagenomic sequencing studies, the intratumoural microbiota has been found as a component of the tumor microenvironment, imperceptibly affecting the tumor progression and response to current antitumor treatments. The underlying carcinogenic mechanisms of intratumoural microbiota, mainly including inducing DNA damages, activating oncogenic signaling pathways and suppressing the immune response, differ significantly in varied organs and are not fully understood. Some native or genetically engineered microbial species can specifically accumulate and replicate within tumors to initiate antitumor immunity, which will be conducive to pursue precise cancer therapies. In this review, we summarized the community characteristics and therapeutic potential of intratumoural microbiota across diverse tumor types. It may provide new insights for a better understanding of tumor biology and hint at the significance of manipulating intratumoural microbiota.


Assuntos
Microbiota/imunologia , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Humanos
11.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445108

RESUMO

Atopic dermatitis (AD) is a common inflammatory dermatosis affecting up to 30% of children and 10% of adults worldwide. AD is primarily driven by an epidermal barrier defect which triggers immune dysregulation within the skin. According to recent research such phenomena are closely related to the microbial dysbiosis of the skin. There is growing evidence that cutaneous microbiota and bacterial biofilms negatively affect skin barrier function, contributing to the onset and exacerbation of AD. This review summarizes the latest data on the mechanisms leading to microbiome dysbiosis and biofilm formation in AD, and the influence of these phenomena on skin barrier function.


Assuntos
Bactérias/imunologia , Biofilmes/crescimento & desenvolvimento , Dermatite Atópica/imunologia , Disbiose/imunologia , Epiderme/imunologia , Microbiota/imunologia , Animais , Disbiose/microbiologia , Humanos , Pele/imunologia
12.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360770

RESUMO

Eosinophils are granulocytes primarily associated with TH2 responses to parasites or immune hyper-reactive states, such as asthma, allergies, or eosinophilic esophagitis. However, it does not make sense from an evolutionary standpoint to maintain a cell type that is only specific for parasitic infections and that otherwise is somehow harmful to the host. In recent years, there has been a shift in the perception of these cells. Eosinophils have recently been recognized as regulators of immune homeostasis and suppressors of over-reactive pro-inflammatory responses by secreting specific molecules that dampen the immune response. Their role during parasitic infections has been well investigated, and their versatility during immune responses to helminths includes antigen presentation as well as modulation of T cell responses. Although it is known that eosinophils can present antigens during viral infections, there are still many mechanistic aspects of the involvement of eosinophils during viral infections that remain to be elucidated. However, are eosinophils able to respond to bacterial infections? Recent literature indicates that Helicobacter pylori triggers TH2 responses mediated by eosinophils; this promotes anti-inflammatory responses that might be involved in the long-term persistent infection caused by this pathogen. Apparently and on the contrary, in the respiratory tract, eosinophils promote TH17 pro-inflammatory responses during Bordetella bronchiseptica infection, and they are, in fact, critical for early clearance of bacteria from the respiratory tract. However, eosinophils are also intertwined with microbiota, and up to now, it is not clear if microbiota regulates eosinophils or vice versa, or how this connection influences immune responses. In this review, we highlight the current knowledge of eosinophils as regulators of pro and anti-inflammatory responses in the context of both infection and naïve conditions. We propose questions and future directions that might open novel research avenues in the future.


Assuntos
Infecções por Bordetella/imunologia , Bordetella bronchiseptica/imunologia , Eosinófilos/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Microbiota/imunologia , Animais , Humanos , Células Th17/imunologia , Células Th2/imunologia
13.
Biomolecules ; 11(8)2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34439831

RESUMO

Wound healing is an essential process to restore tissue integrity after trauma. Large skin wounds such as burns often heal with hypertrophic scarring and contractures, resulting in disfigurements and reduced joint mobility. Such adverse healing outcomes are less common in the oral mucosa, which generally heals faster compared to skin. Several studies have identified differences between oral and skin wound healing. Most of these studies however focus only on a single stage of wound healing or a single cell type. The aim of this review is to provide an extensive overview of wound healing in skin versus oral mucosa during all stages of wound healing and including all cell types and molecules involved in the process and also taking into account environmental specific factors such as exposure to saliva and the microbiome. Next to intrinsic properties of resident cells and differential expression of cytokines and growth factors, multiple external factors have been identified that contribute to oral wound healing. It can be concluded that faster wound closure, the presence of saliva, a more rapid immune response, and increased extracellular matrix remodeling all contribute to the superior wound healing and reduced scar formation in oral mucosa, compared to skin.


Assuntos
Matriz Extracelular/imunologia , Microbiota/imunologia , Mucosa Bucal/lesões , Pele/lesões , Cicatrização/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Matriz Extracelular/química , Fibroblastos/imunologia , Fibroblastos/microbiologia , Regulação da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Queratinócitos/imunologia , Queratinócitos/microbiologia , Macrófagos/imunologia , Macrófagos/microbiologia , Mucosa Bucal/imunologia , Mucosa Bucal/microbiologia , Mucosa Bucal/patologia , Neutrófilos/imunologia , Neutrófilos/microbiologia , Especificidade de Órgãos , Saliva/imunologia , Saliva/microbiologia , Transdução de Sinais , Pele/imunologia , Pele/microbiologia , Pele/patologia
14.
Nat Rev Gastroenterol Hepatol ; 18(10): 731-742, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34400822

RESUMO

Over the past two decades, the importance of the microbiota in health and disease has become evident. Pathological changes to the oral bacterial microbiota, such as those occurring during periodontal disease, are associated with multiple inflammatory conditions, including inflammatory bowel disease. However, the degree to which this association is a consequence of elevated oral inflammation or because oral bacteria can directly drive inflammation at distal sites remains under debate. In this Perspective, we propose that in inflammatory bowel disease, oral disease-associated bacteria translocate to the intestine and directly exacerbate disease. We propose a multistage model that involves pathological changes to the microbial and immune compartments of both the oral cavity and intestine. The evidence to support this hypothesis is critically evaluated and the relevance to other diseases in which oral bacteria have been implicated (including colorectal cancer and liver disease) are discussed.


Assuntos
Inflamação/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Microbiota/imunologia , Boca/microbiologia , Microbioma Gastrointestinal/imunologia , Humanos , Inflamação/imunologia , Doenças Inflamatórias Intestinais/imunologia , Boca/imunologia
15.
Cell Mol Life Sci ; 78(16): 5953-5976, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34223911

RESUMO

SARS-CoV-2 is the virus causing the major pandemic facing the world today. Although, SARS-CoV-2 primarily causes lung infection, a variety of symptoms have proven a systemic impact on the body. SARS-CoV-2 has spread in the community quickly infecting humans from all age, ethnicities and gender. However, fatal outcomes have been linked to specific host factors and co-morbidities such as age, hypertension, immuno-deficiencies, chronic lung diseases or metabolic disorders. A major shift in the microbiome of patients suffering of the coronavirus disease 2019 (COVID-19) have also been observed and is linked to a worst outcome of the disease. As many co-morbidities are already known to be associated with a dysbiosis of the microbiome such as hypertension, diabetes and metabolic disorders. Host factors and microbiome changes are believed to be involved as a network in the acquisition of the infection and the development of the diseases. We will review in detail in this manuscript, the immune response toward SARS-CoV-2 infection as well as the host factors involved in the facilitation and worsening of the infection. We will also address the impact of COVID-19 on the host's microbiome and secondary infection which also worsen the disease.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Pulmão/imunologia , Pulmão/virologia , SARS-CoV-2/imunologia , Replicação Viral/imunologia , Animais , Disbiose/imunologia , Disbiose/virologia , Humanos , Imunidade/imunologia , Microbiota/imunologia , Pandemias
16.
Cancer Immunol Immunother ; 70(12): 3397-3404, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34241677

RESUMO

Fc receptors (FcRs) and the microbiome are both known to have an effect on the development and progression of cancers. Checkpoint inhibitors are a novel class of therapeutics which are used to combat cancer and are integrally linked to both FcRs and the microbiome. The use of checkpoint inhibitors has grown exponentially over the past decade, although many host factors affect both the efficacy and the safety of these therapeutics. Some of these host factors, including the microbiome and the expression of FcRs, are currently being investigated. Here we discuss the current understanding of FcRs (particularly the inhibitory FcγRIIB) and the microbiome in context of T cell immunity, inflammation, cancer, and checkpoint inhibition.


Assuntos
Inibidores de Checkpoint Imunológico/imunologia , Microbiota/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Receptores Fc/imunologia , Animais , Humanos , Imunoterapia/métodos , Inflamação/imunologia
17.
J Immunol ; 207(2): 398-407, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34193598

RESUMO

Alterations in gut microbiota in early life have been associated with the development of asthma; however, the role of gut bacteria or the IgA response to gut bacteria in school-aged children with asthma is unclear. To address this question, we profiled the microbial populations in fecal and nasal swab samples by 16S rRNA sequencing from 40 asthma and 40 control children aged 9-17 y from Peru. Clinical history and laboratory evaluation of asthma and allergy were obtained. Fecal samples were analyzed by flow cytometry and sorted into IgA+ and IgA- subsets for 16S rRNA sequencing. We found that the fecal or nasal microbial 16S rRNA diversity and frequency of IgA+ fecal bacteria did not differ between children with or without asthma. However, the α diversity of fecal IgA+ bacteria was decreased in asthma compared with control. Machine learning analysis of fecal bacterial IgA-enrichment data revealed loss of IgA binding to the Blautia, Ruminococcus, and Lachnospiraceae taxa in children with asthma compared with controls. In addition, this loss of IgA binding was associated with worse asthma control (Asthma Control Test) and increased odds of severe as opposed to mild to moderate asthma. Thus, despite little to no change in the microbiota, children with asthma exhibit an altered host IgA response to gut bacteria compared with control participants. Notably, the signature of altered IgA responses is loss of IgA binding, in particular to members of Clostridia spp., which is associated with greater severity of asthma.


Assuntos
Asma/imunologia , Microbioma Gastrointestinal/imunologia , Imunoglobulina A/imunologia , Adolescente , Bactérias/genética , Bactérias/imunologia , Estudos de Casos e Controles , Criança , Fezes/microbiologia , Feminino , Humanos , Hipersensibilidade/imunologia , Masculino , Microbiota/genética , Microbiota/imunologia , Peru , RNA Ribossômico 16S/genética , Adulto Jovem
18.
Cells ; 10(6)2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200572

RESUMO

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.


Assuntos
COVID-19/diagnóstico , Leucócitos Mononucleares/microbiologia , Pulmão/microbiologia , Microbiota/fisiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Líquido da Lavagem Broncoalveolar/virologia , COVID-19/imunologia , COVID-19/microbiologia , COVID-19/virologia , Estudos de Casos e Controles , Humanos , Leucócitos Mononucleares/virologia , Biópsia Líquida , Pulmão/patologia , Pulmão/virologia , Microbiota/genética , Microbiota/imunologia , Prognóstico , RNA Bacteriano/análise , RNA Fúngico/análise , RNA-Seq , SARS-CoV-2/fisiologia
19.
PLoS One ; 16(7): e0253618, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214099

RESUMO

The proportion of Staphylococcus aureus in the skin microbiome is associated with the severity of inflammation in the skin disease atopic dermatitis. Staphylococcus epidermidis, a commensal skin bacterium, inhibits the growth of S. aureus in the skin. Therefore, the balance between S. epidermidis and S. aureus in the skin microbiome is important for maintaining healthy skin. In the present study, we demonstrated that the heat-treated culture supernatant of Delftia acidovorans, a member of the skin microbiome, inhibits the growth of S. epidermidis, but not that of S. aureus. Comprehensive gene expression analysis by RNA sequencing revealed that culture supernatant of D. acidovorans increased the expression of genes related to glycolysis and the tricarboxylic acid cycle (TCA) cycle in S. epidermidis. Malonate, an inhibitor of succinate dehydrogenase in the TCA cycle, suppressed the inhibitory effect of the heat-treated culture supernatant of D. acidovorans on the growth of S. epidermidis. Reactive oxygen species production in S. epidermidis was induced by the heat-treated culture supernatant of D. acidovorans and suppressed by malonate. Further, the inhibitory effect of the heat-treated culture supernatant of D. acidovorans on the growth of S. epidermidis was suppressed by N-acetyl-L-cysteine, a free radical scavenger. These findings suggest that heat-resistant substances secreted by D. acidovorans inhibit the growth of S. epidermidis by inducing the production of reactive oxygen species via the TCA cycle.


Assuntos
Delftia acidovorans/imunologia , Dermatite Atópica/imunologia , Pele/microbiologia , Infecções Estafilocócicas/imunologia , Staphylococcus epidermidis/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Ciclo do Ácido Cítrico/imunologia , Delftia acidovorans/genética , Delftia acidovorans/metabolismo , Dermatite Atópica/microbiologia , Dermatite Atópica/patologia , Regulação Bacteriana da Expressão Gênica/imunologia , Humanos , Microbiota/imunologia , RNA-Seq , Espécies Reativas de Oxigênio/metabolismo , Pele/imunologia , Pele/patologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/imunologia , Staphylococcus aureus/isolamento & purificação , Staphylococcus epidermidis/imunologia
20.
J Dermatol Sci ; 102(3): 142-157, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34116898

RESUMO

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by eczematous and pruritic skin lesions. In recent decades, the prevalence of AD has increased worldwide, most notably in developing countries. The enormous progress in our understanding of the complex composition and functions of the epidermal barrier allows for a deeper appreciation of the active role that the skin barrier plays in the initiation and maintenance of skin inflammation. The epidermis forms a physical, chemical, immunological, neuro-sensory, and microbial barrier between the internal and external environment. Not only lesional, but also non-lesional areas of AD skin display many morphological, biochemical and functional differences compared with healthy skin. Supporting this notion, genetic defects affecting structural proteins of the skin barrier, including filaggrin, contribute to an increased risk of AD. There is evidence to suggest that natural environmental allergens and man-made pollutants are associated with an increased likelihood of developing AD. A compromised epidermal barrier predisposes the skin to increased permeability of these compounds. Numerous topical and systemic therapies for AD are currently available or in development; while anti-inflammatory therapy is central to the treatment of AD, some existing and novel therapies also appear to exert beneficial effects on skin barrier function. Further research on the skin barrier, particularly addressing epidermal differentiation and inflammation, lipid metabolism, and the role of bacterial communities for skin barrier function, will likely expand our understanding of the complex etiology of AD and lead to identification of novel targets and the development of new therapies.


Assuntos
Dermatite Atópica/imunologia , Fármacos Dermatológicos/farmacocinética , Epiderme/patologia , Microbiota/imunologia , Diferenciação Celular/efeitos dos fármacos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Fármacos Dermatológicos/uso terapêutico , Desenvolvimento de Medicamentos , Epiderme/efeitos dos fármacos , Epiderme/imunologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/imunologia , Microbiota/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Perda Insensível de Água/efeitos dos fármacos , Perda Insensível de Água/imunologia
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