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1.
Acta Biomater ; 137: 305-315, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34678484

RESUMO

Considered as some of the most devastating complications, Cutibacterium acnes (C. acnes)-related osteomyelitis are among the hardest infections to diagnose and treat. Mesenchymal stem cells (MSCs) secrete number of immunomodulatory and antimicrobial soluble factors, making them an attractive treatment for bacterial infection. In this study, we examined MSCs/C. acnes interaction and analyzed the subsequent MSCs and bacteria's behaviors. Human bone marrow-derived MSCs were infected by C. acnes clinical strain harvested from non-infected bone site. Following 3 h of interaction, around 4% of bacteria were found in the intracellular compartment. Infected MSCs increased the secretion of prostaglandin E2 and indolamine 2,3 dioxygenase immunomodulatory mediators. Viable intracellular bacteria analyzed by infrared spectroscopy and atomic force microscopy revealed deep modifications in the wall features. In comparison with unchallenged bacteria, the viable intracellular bacteria showed (i) an increase in biofilm formation on orthopaedical-based materials, (ii) an increase in the invasiveness of osteoblasts and (iii) persistence in macrophage, suggesting the acquisition of virulence factors. Overall, these results showed a direct impact of C. acnes on bone marrow-derived MSCs, suggesting that blocking the C. acnes/MSCs interactions may represent an important new approach to manage chronic osteomyelitis infections. STATEMENT OF SIGNIFICANCE: The interaction of bone commensal C. acnes with bone marrow mesenchymal stem cells induces modifications in C. acnes wall characteristics. These bacteria increased (i) the biofilm formation on orthopaedical-based materials, (ii) the invasiveness of bone forming cells and (iii) the resistance to macrophage clearance through the modification of the wall nano-features and/or the increase in catalase production.


Assuntos
Células-Tronco Mesenquimais , Osteomielite , Biofilmes , Células da Medula Óssea , Humanos , Propionibacterium acnes , Próteses e Implantes
2.
Clin Immunol ; 177: 18-28, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26598010

RESUMO

Immune thrombocytopenic purpura (ITP) is a disease characterized by antibody-mediated platelet destruction. The T- and B-cell subsets have been extensively studied in primary ITP, but the NK cell compartment has been less thoroughly explored. We investigated the NK cell receptor repertoire and the functionality of NK cells in the peripheral blood and spleen in patients with primary ITP. An immunophenotypic analysis of peripheral blood lymphocytes from patients revealed that the numbers of CD19+ B lymphocytes, CD4+ and CD8+ T lymphocytes and CD3-CD56+ NK cells were within the normal range. No major alteration to the expression of distinct inhibitory or activating NK cell receptors was observed. The functionality of NK cells, as evaluated by their ability to degranulate in conditions of natural cytotoxicity or antibody-dependent cell cytotoxicity (ADCC), was preserved in these patients. By contrast, these stimuli induced lower levels of IFNγ production by the NK cells of ITP patients than by those of healthy controls. We then compared the splenic NK cell functions of ITP patients with those of cadaveric heart-beating donors (CHBD) as controls. The splenic NK cells of ITP patients tended to be less efficient in natural cytotoxicity conditions and more efficient in ADCC conditions than control splenic NK cells. Finally, we found that infusions of intravenous immunoglobulin led to the inhibition of NK cell activation through the modulation of the interface between target cells and NK cells.


Assuntos
Células Matadoras Naturais/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Humanos , Imunoglobulinas Intravenosas/farmacologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Interferon gama/sangue , Interferon gama/imunologia , Células K562 , Células Matadoras Naturais/efeitos dos fármacos , Leucócitos Mononucleares , Masculino , Camundongos , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Baço/citologia , Baço/imunologia , Adulto Jovem
3.
Br J Dermatol ; 166(4): 789-96, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22233261

RESUMO

BACKGROUND: Psoriasis and atopic dermatitis are the most recurrent skin inflammatory disorders. Despite their distinct aetiology and clinical aspects, these diseases share several immunological features. Besides the largely documented role of T cells, emerging literature supports a potential involvement of innate immune effectors, the natural killer (NK) cells, in both pathologies. In the peripheral blood, NK cells consist of CD3-CD56dim and CD3-CD56bright cell subsets, harbouring a distinct cell surface phenotype, but both endowed with the main NK-cell effector functions: cytotoxicity and cytokine production. OBJECTIVES: To determine whether the frequency, the cell surface phenotype and the functional properties of peripheral NK cells were affected in patients with psoriasis or atopic dermatitis. METHODS: Peripheral blood mononuclear cells were isolated from 11 patients with psoriasis, nine patients with atopic dermatitis and 16 healthy individuals. By using flow cytometry, we analysed the following parameters of peripheral NK cells: the frequency, the cell surface expression of several NK-cell receptors (NKR) and the activation of the effector functions upon various in vitro stimuli. RESULTS: Peripheral NK cells were significantly reduced in both skin diseases. The cell surface expression of various NKR was differently modified in peripheral NK cells of the two cohorts of patients. Finally, NK-cell natural cytotoxicity was affected only in atopic dermatitis, while interferon-γ production was defective in both groups of patients. CONCLUSION: Psoriasis and atopic dermatitis are associated with quantitative and qualitative changes of peripheral NK cells, mostly shared by both diseases, supporting a common process implicating these innate effectors in skin inflammation.


Assuntos
Dermatite Atópica/imunologia , Células Matadoras Naturais/imunologia , Psoríase/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
4.
Clin Exp Allergy ; 41(5): 657-64, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21375605

RESUMO

BACKGROUND: Delayed reactions to iodine contrast media (CM) account for 1-3% of patients with adverse reactions to iodine CM. The cellular and molecular mechanisms of these reactions remain poorly documented. Although most of these reactions are T cell mediated, the involvement of dendritic cells (DC) has not been investigated sufficiently. OBJECTIVE: To determine whether the T cell response to iodixanol requires DC as antigen-presenting cell and, more particularly, to evaluate the changes induced by iodixanol on DC maturation and in vitro production of cytokines after drug stimulation in patients with maculopapular exanthema. METHODS: Peripheral blood lymphocytes, immature monocyte-derived DC (imDC) and skin biopsies were obtained from patients with delayed reactions to iodixanol and tolerant subjects. We studied the consequences of the interaction between DC, lymphocytes and iodixanol by phenotype analysis, proliferation and cytokine production. RESULTS: A T-cell-mediated reaction was evidenced in patient biopsies, with a lymphocyte-rich, peri-vascular infiltrate. Iodixanol induced maturation of imDC from patients but not from controls, with expression of the co-stimulatory markers CD83, CD86 and CD40 and an increase in mean fluorescence intensity of CD80, CD86 and HLA-DR. In the absence of DC, positive cell proliferation to iodixanol was detected in only one patient while the addition of DC produced a positive test in five of the six patients. Similarly, the increase in cytokines (IFN-γ, IL-2, IL-6, IL-1b and TNF-α) was higher when imDC were introduced into the culture together with the culprit drug. CONCLUSION AND CLINICAL RELEVANCE: These results provide evidence for a DC-mediated mechanism in delayed allergic reactions to CM, influencing T cell proliferation and cytokine production. These new insights will be helpful for designing immunotherapeutic strategies and in vitro diagnostic tests of CM-delayed reactions.


Assuntos
Meios de Contraste/efeitos adversos , Células Dendríticas/imunologia , Hipersensibilidade Tardia/imunologia , Ácidos Tri-Iodobenzoicos/imunologia , Idoso de 80 Anos ou mais , Proliferação de Células/efeitos dos fármacos , Citocinas/biossíntese , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/patologia , Humanos , Hipersensibilidade Tardia/diagnóstico , Compostos de Iodo/efeitos adversos , Compostos de Iodo/imunologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Testes Cutâneos , Ácidos Tri-Iodobenzoicos/administração & dosagem
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