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1.
J Bone Joint Surg Am ; 106(18): 1697-1703, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-38950104

RESUMO

BACKGROUND: An emerging paradigm suggests that positive Cutibacterium acnes shoulder cultures can result from either true infection or contamination, with true infections demonstrating a host inflammatory response and early culture growth. This clinical retrospective study examines the relationship between C. acnes antigen, C. acnes culture results, and inflammation. METHODS: From January 2021 to July 2023, 1,365 periprosthetic synovial fluid samples from 347 institutions were tested for shoulder infection at a centralized clinical laboratory. A biomarker scoring system based on the 2018 International Consensus Meeting (ICM) definition was utilized to assign each sample an inflammation score. Associations between inflammation, culture results, and C. acnes antigen results were assessed utilizing cluster and correlation analyses. RESULTS: Of 1,365 samples, 1,150 were culture-negative and 215 were culture-positive (94 C. acnes and 121 other organisms). Among the 94 C. acnes culture-positive samples, unsupervised clustering revealed 2 distinct sample clusters (silhouette coefficient, 0.83): a high-inflammation cluster (n = 67) and a low-inflammation cluster (n = 27). C. acnes antigen levels demonstrated moderate-strong positive correlation with inflammation (Spearman ρ, 0.60), with 166-fold higher levels of C. acnes antigen in high-inflammation samples (16.6 signal/cutoff [S/CO]) compared with low-inflammation samples (0.1 S/CO) (p < 0.0001). The days to C. acnes culture positivity demonstrated weak-inverse correlation with inflammation (Spearman ρ = -0.38), with 1.5-fold earlier growth among the 67 high-inflammation samples (6.7 compared with 10.4 days; p < 0.0001). Elevated C. acnes antigen was observed in only 4 (0.38%) of 1,050 low-inflammation culture-negative samples and in only 5 (4.9%) of 103 high-inflammation non- C. acnes -positive cultures. However, 19.0% of high-inflammation, culture-negative samples demonstrated elevated C. acnes antigen. CONCLUSIONS: Synovial fluid C. acnes antigen was detected among shoulder samples with high inflammation and early culture growth, supporting the emerging paradigm that these samples represent true infection. Future research should explore antigen testing to differentiate contamination from infection and to identify culture-negative C. acnes infections. LEVEL OF EVIDENCE: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Antígenos de Bactérias , Infecções por Bactérias Gram-Positivas , Propionibacterium acnes , Líquido Sinovial , Humanos , Estudos Retrospectivos , Líquido Sinovial/microbiologia , Líquido Sinovial/imunologia , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/imunologia , Antígenos de Bactérias/análise , Antígenos de Bactérias/imunologia , Masculino , Propionibacterium acnes/isolamento & purificação , Propionibacterium acnes/imunologia , Feminino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/diagnóstico , Idoso , Inflamação/microbiologia , Articulação do Ombro/microbiologia , Articulação do Ombro/imunologia , Propionibacteriaceae/isolamento & purificação , Propionibacteriaceae/imunologia
2.
Microbiol Res ; 285: 127749, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38761490

RESUMO

Among 5 types of the Christie-Atkins-Munch-Petersen factor (CAMP) of Cutibacterium acnes, CAMP1 is highly expressed in phylotype II as well as IB, and thought to be a virulence factor of opportunistic but fatal blood, soft tissue, and implant-related infections. The target of a human single-chain variable antibody fragment (scFv), recently isolated from a phage display library, has been identified as CAMP1 of phylotype II, using immunoprecipitation followed by mass spectrometry, phage display peptide biopanning, 3D-modelling, and ELISA. The IgG1 format of the antibody could enhance phagocytosis of C. acnes DMST 14916 by THP-1 human monocytes. Our results suggest that the antibody-dependent phagocytosis process is mediated by the caveolae membrane system and involves the induction of IL-1ß. This is the first report on the study of a human antibody against CAMP1 of C. acnes phylotype II, of which a potential use as therapeutic antibody against virulence C. acnes infection is postulated.


Assuntos
Imunoglobulina G , Macrófagos , Fagocitose , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Imunoglobulina G/imunologia , Interleucina-1beta/metabolismo , Interleucina-1beta/imunologia , Células THP-1 , Fatores de Virulência/imunologia , Anticorpos Antibacterianos/imunologia , Monócitos/imunologia , Monócitos/microbiologia , Anticorpos de Cadeia Única/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/genética , Propionibacteriaceae/imunologia
3.
Microbiol Spectr ; 9(3): e0149721, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34937192

RESUMO

Tumors and infectious agents both benefit from an immunosuppressive environment. Cutibacterium acnes (C. acnes) is a bacterium in the normal skin microbiota, which has the ability to survive intracellularly in macrophages and is significantly more common in prostate cancer tissue compared with normal prostate tissue. This study investigated if prostate cancer tissue culture positive for C. acnes has a higher infiltration of regulatory T-cells (Tregs) and if macrophages stimulated with C. acnes induced the expression of immunosuppressive genes that could be linked to an increase of Tregs in prostate cancer. Real-time PCR and enzyme-linked immunosorbent spot assay (ELISA) were used to examine the expression of immunosuppressive genes in human macrophages stimulated in vitro with C. acnes, and associations between the presence of C. acnes and infiltration of Tregs were investigated by statistically analyzing data generated in two previous studies. The in vitro results demonstrated that macrophages stimulated with C. acnes significantly increased their expression of PD-L1, CCL17, and CCL18 mRNA and protein (p <0.05). In the cohort, Tregs in tumor stroma and tumor epithelia were positively associated with the presence of C. acnes (P = 0.0004 and P = 0.046, respectively). Since the macrophages stimulated with C. acnes in vitro increased the expression of immunosuppressive genes, and prostate cancer patients with prostatic C. acnes infection had higher infiltration of Tregs than their noninfected counterparts, we suggest that C. acnes may contribute to an immunosuppressive tumor environment that is vital for prostate cancer progression. IMPORTANCE In an immune suppressive tumor microenvironment constituted by immunosuppressive cells and immunosuppressive mediators, tumors may improve their ability to give rise to a clinically relevant cancer. In the present study, we found that C. acnes might contribute to an immunosuppressive environment by recruiting Tregs and by increasing the expression of immunosuppressive mediators such as PD-L1, CCL17, and CCL18. We believe that our data add support to the hypothesis of a contributing role of C. acnes in prostate cancer development. If established that C. acnes stimulates prostate cancer progression it may open up avenues for targeted prostate cancer treatment.


Assuntos
Tolerância Imunológica/imunologia , Macrófagos/imunologia , Propionibacteriaceae/imunologia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/microbiologia , Linfócitos T Reguladores/imunologia , Antígeno B7-H1/biossíntese , Antígeno B7-H1/genética , Quimiocina CCL17/biossíntese , Quimiocina CCL17/genética , Quimiocinas CC/biossíntese , Quimiocinas CC/genética , ELISPOT , Humanos , Tolerância Imunológica/genética , Masculino , Microbiota/imunologia , Neoplasias da Próstata/patologia , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia
4.
Int J Med Sci ; 18(5): 1114-1120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33526970

RESUMO

Bacteria response to their environment by producing some compounds which are used in cosmetic and pharmaceutical applications. Some probiotics can regulate immune response and modulate the symptoms of several diseases. Bacteria affect skin response to skin care products. Bacteria are thought to play an important role in acne incidence, skin moisture, and nutrient metabolism, but only a few studies have focused on the extracts of Lactobacillus plantarum in skin care. In this study, we identified that L. plantarum-GMNL6 enhanced collagen synthesis and the gene expression of serine palmitoyltransferase small subunit A. Meanwhile, L. plantarum-GMNL6 reduced the melanin synthesis, the biofilm of Staphylococcus aureus, and the proliferation of Cutibacterium acnes. Information from clinical observation during the ointment for external face use in people displayed that the syndromes of skin moisture, skin color, spots, wrinkles, UV spots, and porphyrins were improved. The diversification of human skin microbiomes was affected by smearing the face of volunteers with L. plantarum-GMNL6. Understanding the potential mechanisms of the action of L. plantarum-GMNL6 in dermatologic conditions promotes the development of care products.


Assuntos
Lactobacillus plantarum/imunologia , Microbiota/imunologia , Probióticos/administração & dosagem , Higiene da Pele/métodos , Pele/microbiologia , Adulto , Animais , Biofilmes/crescimento & desenvolvimento , Linhagem Celular Tumoral , Colágeno/biossíntese , Feminino , Fibroblastos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Pomadas , Propionibacteriaceae/crescimento & desenvolvimento , Propionibacteriaceae/imunologia , Propionibacteriaceae/isolamento & purificação , Pele/imunologia , Pele/metabolismo , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/imunologia , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento , Adulto Jovem
5.
G Ital Dermatol Venereol ; 155(6): 711-718, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33084268

RESUMO

Acne fulminans (AF) is a rare and severe form of inflammatory acne presenting clinically with an abrupt outburst of painful, hemorrhagic pustules and ulceration, that may or may not be associated with systemic symptoms, such as fever, polyarthritis, and laboratory abnormalities. It typically affects male teenagers with a pre-existing acne. Although the pathogenetic mechanism has not been established yet, a role of genetic, abnormal immunologic response, drugs intake, hormonal imbalance and viral infection, as causal factors, has been identified. AF may occur as a single disease or may be associated with other disorders. Traditionally, AF has been classified, on the basis of the presence of systemic involvement, in "acne fulminans" and acne fulminans "sine fulminans," when no systemic involvement is present. Recently, four clinical variants have been proposed: acne fulminans with systemic symptoms (AF-SS), acne fulminans without systemic symptoms (AF-WOSS), isotretinoin-induced acne fulminans with systemic symptoms (IIAF-SS), isotretinoin-induced acne fulminans without systemic symptoms (IIAF-WOSS). The diagnosis of AF is usually based on clinical history and physical examination. No specific laboratory abnormalities are generally found. In selected cases, biopsy and/or radiologic imaging are helpful for a correct diagnosis. The treatment significantly differs from severe acne according to severity of clinical presentation and possible systemic involvement. Currently, systemic corticosteroids (prednisolone) and retinoids (isotretinoin) represent the first choice of treatment. Dapsone, cyclosporine A, methotrexate, azathioprine, levamisole, and biological agents such as anakinra, infliximab, adalimumab may be considered as alternative therapies in selected cases. Adjunctive topical and physical therapies may also be considered.


Assuntos
Acne Vulgar , Acne Vulgar/complicações , Acne Vulgar/diagnóstico , Acne Vulgar/fisiopatologia , Acne Vulgar/terapia , Síndrome de Hiperostose Adquirida/complicações , Síndrome de Hiperostose Adquirida/diagnóstico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Androgênios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Artralgia/complicações , Terapia Combinada , Desbridamento , Fármacos Dermatológicos/uso terapêutico , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Inflamação , Isotretinoína/efeitos adversos , Isotretinoína/uso terapêutico , Lasers de Corante , Terapia com Luz de Baixa Intensidade , Masculino , Fotoquimioterapia , Propionibacteriaceae/imunologia , Retinoides/uso terapêutico , Avaliação de Sintomas , Adulto Jovem
6.
J Clin Invest ; 130(3): 1417-1430, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-31805013

RESUMO

Epidermal growth factor receptor (EGFR) and MEK inhibitors (EGFRi/MEKi) are beneficial for the treatment of solid cancers but are frequently associated with severe therapy-limiting acneiform skin toxicities. The underlying molecular mechanisms are poorly understood. Using gene expression profiling we identified IL-36γ and IL-8 as candidate drivers of EGFRi/MEKi skin toxicity. We provide molecular and translational evidence that EGFRi/MEKi in concert with the skin commensal bacterium Cutibacterium acnes act synergistically to induce IL-36γ in keratinocytes and subsequently IL-8, leading to cutaneous neutrophilia. IL-36γ expression was the combined result of C. acnes-induced NF-κB activation and EGFRi/MEKi-mediated expression of the transcription factor Krüppel-like factor 4 (KLF4), due to the presence of both NF-κB and KLF4 binding sites in the human IL-36γ gene promoter. EGFRi/MEKi increased KLF4 expression by blockade of the EGFR/MEK/ERK pathway. These results provide an insight into understanding the pathological mechanism of the acneiform skin toxicities induced by EGFRi/MEKi and identify IL-36γ and the transcription factor KLF4 as potential therapeutic targets.


Assuntos
Receptores ErbB/imunologia , Interleucina-1/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Propionibacteriaceae/imunologia , Dermatopatias Bacterianas/imunologia , Animais , Receptores ErbB/genética , Humanos , Interleucina-1/genética , Queratinócitos/imunologia , Queratinócitos/microbiologia , Queratinócitos/patologia , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/imunologia , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Camundongos Knockout , NF-kappa B/genética , NF-kappa B/imunologia , Dermatopatias Bacterianas/genética , Dermatopatias Bacterianas/patologia
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