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1.
J Leukoc Biol ; 115(3): 536-546, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-37992073

RESUMO

Candida albicans belongs to our commensal mucosal flora and in immune-competent individuals in the absence of epithelial damage, this fungus is well tolerated and controlled by our immune defense. However, C. albicans is an opportunistic microorganism that can cause different forms of infections, ranging from superficial to life-threatening systemic infections. C. albicans is polymorphic and switches between different phenotypes (e.g. from yeast form to hyphal form). C. albicans hyphae are invasive and can grow into tissues to eventually reach circulation. During fungal infections, neutrophils in particular play a critical role for the defense, but how neutrophils are directed toward the invasive forms of fungi is less well understood. We set out to investigate possible neutrophil chemoattractants released by C. albicans into culture supernatants. We found that cell-free culture supernatants from the hyphal form of C. albicans induced both neutrophil chemotaxis and concomitant intracellular calcium transients. Size separation and hydrophobic sorting of supernatants indicated small hydrophilic factors as responsible for the activity. Further analysis showed that the culture supernatants contained high levels of short-chain fatty acids with higher levels from hyphae as compared to yeast. Short-chain fatty acids are known neutrophil chemoattractants acting via the neutrophil free fatty acid receptor 2. In line with this, the calcium signaling in neutrophils induced by hyphae culture supernatants was blocked by a free fatty acid receptor 2 antagonist and potently increased in the presence of a positive allosteric modulator. Our data imply that short-chain fatty acids may act as a recruitment signal whereby neutrophils can detect C. albicans hyphae.


Assuntos
Candida albicans , Neutrófilos , Humanos , Ácidos Graxos não Esterificados/análise , Hifas/química , Hifas/genética , Quimiotaxia , Ácidos Graxos Voláteis/análise , Fatores Quimiotáticos
2.
PLoS Pathog ; 19(11): e1011677, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37917600

RESUMO

Candida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report that put1-/- and put2-/- strains, carrying defective Proline UTilization genes, display remarkable proline sensitivity with put2-/- mutants being hypersensitive due to the accumulation of the toxic intermediate pyrroline-5-carboxylate (P5C), which inhibits mitochondrial respiration. The put1-/- and put2-/- mutations attenuate virulence in Drosophila and murine candidemia models and decrease survival in human neutrophils and whole blood. Using intravital 2-photon microscopy and label-free non-linear imaging, we visualized the initial stages of C. albicans cells infecting a kidney in real-time, directly deep in the tissue of a living mouse, and observed morphological switching of wildtype but not of put2-/- cells. Multiple members of the Candida species complex, including C. auris, are capable of using proline as a sole energy source. Our results indicate that a tailored proline metabolic network tuned to the mammalian host environment is a key feature of opportunistic fungal pathogens.


Assuntos
Candida albicans , Saccharomyces cerevisiae , Animais , Camundongos , Humanos , Virulência , Saccharomyces cerevisiae/genética , Prolina/metabolismo , Candida , Mamíferos
3.
EMBO Rep ; 24(11): e57571, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37795769

RESUMO

The peptide toxin candidalysin, secreted by Candida albicans hyphae, promotes stimulation of neutrophil extracellular traps (NETs). However, candidalysin alone triggers a distinct mechanism for NET-like structures (NLS), which are more compact and less fibrous than canonical NETs. Candidalysin activates NADPH oxidase and calcium influx, with both processes contributing to morphological changes in neutrophils resulting in NLS formation. NLS are induced by leucotoxic hypercitrullination, which is governed by calcium-induced protein arginine deaminase 4 activation and initiation of intracellular signalling events in a dose- and time-dependent manner. However, activation of signalling by candidalysin does not suffice to trigger downstream events essential for NET formation, as demonstrated by lack of lamin A/C phosphorylation, an event required for activation of cyclin-dependent kinases that are crucial for NET release. Candidalysin-triggered NLS demonstrate anti-Candida activity, which is resistant to nuclease treatment and dependent on the deprivation of Zn2+ . This study reveals that C. albicans hyphae releasing candidalysin concurrently trigger canonical NETs and NLS, which together form a fibrous sticky network that entangles C. albicans hyphae and efficiently inhibits their growth.


Assuntos
Candida albicans , Armadilhas Extracelulares , Candida albicans/metabolismo , Armadilhas Extracelulares/metabolismo , Cálcio/metabolismo , Proteínas Fúngicas/metabolismo
4.
EBioMedicine ; 85: 104292, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36182774

RESUMO

BACKGROUND: The hard endpoint of death is one of the most significant outcomes in both clinical practice and research settings. Our goal was to discover direct causes of longevity from medically accessible data. METHODS: Using a framework that combines local causal discovery algorithms with discovery of maximally predictive and compact feature sets (the "Markov boundaries" of the response) and equivalence classes, we examined 186 variables and their relationships with survival over 27 years in 1507 participants, aged ≥71 years, of the longitudinal, community-based D-EPESE study. FINDINGS: As few as 8-15 variables predicted longevity at 2-, 5- and 10-years with predictive performance (area under receiver operator characteristic curve) of 0·76 (95% CIs 0·69, 0·83), 0·76 (0·72, 0·81) and 0·66 (0·61, 0·71), respectively. Numbers of small high-density lipoprotein particles, younger age, and fewer pack years of cigarette smoking were the strongest determinants of longevity at 2-, 5- and 10-years, respectively. Physical function was a prominent predictor of longevity at all time horizons. Age and cognitive function contributed to predictions at 5 and 10 years. Age was not among the local 2-year prediction variables (although significant in univariable analysis), thus establishing that age is not a direct cause of 2-year longevity in the context of measured factors in our data that determine longevity. INTERPRETATION: The discoveries in this study proceed from causal data science analyses of deep clinical and molecular phenotyping data in a community-based cohort of older adults with known lifespan. FUNDING: NIH/NIA R01AG054840, R01AG12765, and P30-AG028716, NIH/NIA Contract N01-AG-12102 and NCRR 1UL1TR002494-01.


Assuntos
Exercício Físico , Longevidade , Humanos , Idoso , Estudos de Coortes
5.
Sensors (Basel) ; 22(10)2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35632052

RESUMO

This paper details how to construct a small-scale shaking table attached to a magnetorheological (MR) damper. The motivation for this construction relies on the increasing interest in modeling the dynamics of MR dampers-MR dampers have been used in structures for safety reasons. To model the MR damper, we use the so-called 'Dahl model', which is useful to represent systems with a hysteresis. The Dahl model, validated through experimental data collected in a laboratory, was combined with a linear model to represent a two-story building. This two-story building model allows us to simulate the dynamics of that building when its floors are attached to MR dampers. By doing so, we can assess-through simulation-to what extent MR dampers can protect structures from vibrations. Using data from the 'El Centro' earthquake (1940), we can conclude that MR dampers have the potential to reduce the impact of earthquakes upon structures. This finding emphasizes the potential benefits of MR dampers for the safety of structures, which is a conclusion taken from the apparatus detailed in this paper.


Assuntos
Terremotos , Vibração , Simulação por Computador
6.
J. bras. nefrol ; 43(3): 431-433, July-Sept. 2021. graf
Artigo em Inglês, Português | LILACS | ID: biblio-1340123

RESUMO

Abstract The Phagocytosis of fungal structures by neutrophils is a well-documented function of these immune cells. However, neutrophil phagocytosis of hyphal structures in the urine sediment is not usually observed during routine sample evaluation. This is a case of hyphal phagocytosis by neutrophils in the urine of a kidney allograft recipient patient.


Resumo A fagocitose de estruturas fúngicas por neutrófilos é uma função bem documentada destas células imunes. No entanto, a fagocitose de hifas por neutrófilos no sedimento urinário não é normalmente observada durante avaliação de rotina de amostras. Este é um caso de fagocitose de hifas por neutrófilos na urina de um paciente receptor de aloenxerto renal.


Assuntos
Humanos , Hifas , Neutrófilos , Fagocitose
7.
Front Chem ; 9: 666853, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124001

RESUMO

Interaction between microorganisms and their surroundings are generally mediated via the cell wall or cell envelope. An understanding of the overall chemical composition of these surface layers may give clues on how these interactions occur and suggest mechanisms to manipulate them. This knowledge is key, for instance, in research aiming to reduce colonization of medical devices and device-related infections from different types of microorganisms. In this context, X-ray photoelectron spectroscopy (XPS) is a powerful technique as its analysis depth below 10 nm enables studies of the outermost surface structures of microorganism. Of specific interest for the study of biological systems is cryogenic XPS (cryo-XPS). This technique allows studies of intact fast-frozen hydrated samples without the need for pre-treatment procedures that may cause the cell structure to collapse or change due to the loss of water. Previously, cryo-XPS has been applied to study bacterial and algal surfaces with respect to their composition of lipids, polysaccharides and peptide (protein and/or peptidoglycan). This contribution focuses onto two other groups of microorganisms with widely different architecture and modes of life, namely fungi and viruses. It evaluates to what extent existing models for data treatment of XPS spectra can be applied to understand the chemical composition of their very different surface layers. XPS data from model organisms as well as reference substances representing specific building blocks of their surface were collected and are presented. These results aims to guide future analysis of the surface chemical composition of biological systems.

8.
Front Immunol ; 12: 553911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717058

RESUMO

Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8/A9 during ICTD and fungal clearance were investigated. S100A8/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8/A9 could serve as promising adjunct therapy against this challenging disease.


Assuntos
Calgranulina A/metabolismo , Calgranulina B/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Micoses/etiologia , Micoses/metabolismo , Peritonite/etiologia , Peritonite/metabolismo , Animais , Biomarcadores , Contagem de Colônia Microbiana , Citocinas/metabolismo , Modelos Animais de Doenças , Resistência à Doença/genética , Resistência à Doença/imunologia , Suscetibilidade a Doenças , Imunomodulação , Mediadores da Inflamação , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Micoses/mortalidade , Micoses/patologia , Peritonite/mortalidade , Peritonite/patologia , Prognóstico
10.
J Bras Nefrol ; 43(3): 431-433, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33350430

RESUMO

The Phagocytosis of fungal structures by neutrophils is a well-documented function of these immune cells. However, neutrophil phagocytosis of hyphal structures in the urine sediment is not usually observed during routine sample evaluation. This is a case of hyphal phagocytosis by neutrophils in the urine of a kidney allograft recipient patient.


Assuntos
Hifas , Neutrófilos , Humanos , Fagocitose
11.
Curr Opin Microbiol ; 58: 106-115, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33091824

RESUMO

Opportunistic, invasive mycoses in immunocompromised patients remain challenging for health care with unacceptably high levels of morbidity and mortality. Neutrophils are essential in host protection against invasive mycoses. Upon development of acute infection, neutrophils are recruited from circulation to the infected tissue, where they exert a considerable variety of effector functions with the ultimate task to eradicate invading microbes. Effector functions include recognition, phagocytosis and intracellular killing of microorganisms via oxidative and non-oxidative mechanisms, excretion of antimicrobial factors from intracellular storages (degranulation), release of neutrophil extracellular traps (NETs) and of extracellular vesicles (EVs), as well as generation of cytokines and chemokines to modulate immune responses. Herein, we describe recent findings which further our understanding of the roles of neutrophils during opportunistic fungal infections which could serve as starting point for the development of immune-targeted interventions to improve clinical management of affected individuals.


Assuntos
Fungos/fisiologia , Micoses/imunologia , Neutrófilos/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Armadilhas Extracelulares/imunologia , Fungos/genética , Humanos , Micoses/genética , Micoses/microbiologia , Fagocitose
12.
Nature ; 581(7807): 152-158, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32405005

RESUMO

Bound three-body quantum systems are important for fundamental physics1,2 because they enable tests of quantum electrodynamics theory and provide access to the fundamental constants of atomic physics and to nuclear properties. Molecular hydrogen ions, the simplest molecules, are representative of this class3. The metastability of the vibration-rotation levels in their ground electronic states offers the potential for extremely high spectroscopic resolution. Consequently, these systems provide independent access to the Rydberg constant (R∞), the ratios of the electron mass to the proton mass (me/mp) and of the electron mass to the deuteron mass (me/md), the proton and deuteron nuclear radii, and high-level tests of quantum electrodynamics4. Conventional spectroscopy techniques for molecular ions5-14 have long been unable to provide precision competitive with that of ab initio theory, which has greatly improved in recent years15. Here we improve our rotational spectroscopy technique for a sympathetically cooled cluster of molecular ions stored in a linear radiofrequency trap16 by nearly two orders in accuracy. We measured a set of hyperfine components of the fundamental rotational transition. An evaluation resulted in the most accurate test of a quantum-three-body prediction so far, at the level of 5 × 10-11, limited by the current uncertainties of the fundamental constants. We determined the value of the fundamental constants combinations [Formula: see text] and mp/me with a fractional uncertainty of 2 × 10-11, in agreement with, but more precise than, current Committee on Data for Science and Technology values. These results also provide strong evidence of the correctness of previous key high-precision measurements and a more than 20-fold stronger bound for a hypothetical fifth force between a proton and a deuteron.

14.
Front Microbiol ; 10: 1843, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31481939

RESUMO

Invasive mycoses remain underdiagnosed and difficult to treat. Hospitalized individuals with compromised immunity increase in number and constitute the main risk group for severe fungal infections. Current antifungal therapy is hampered by slow and insensitive diagnostics and frequent toxic side effects of standard antifungal drugs. Identification of new antifungal compounds with high efficacy and low toxicity is therefore urgently required. We investigated the antifungal activity of tempol, a cell-permeable nitroxide. To narrow down possible mode of action we used RNA-seq technology and metabolomics to probe for pathways specifically disrupted in the human fungal pathogen Candida albicans due to tempol administration. We found genes upregulated which are involved in iron homeostasis, mitochondrial stress, steroid synthesis, and amino acid metabolism. In an ex vivo whole blood infection, tempol treatment reduced C. albicans colony forming units and at the same time increased the release of pro-inflammatory cytokines, such as interleukin 8 (IL-8, monocyte chemoattractant protein-1, and macrophage migration inhibitory factor). In a systemic mouse model, tempol was partially protective with a significant reduction of fungal burden in the kidneys of infected animals during infection onset. The results obtained propose tempol as a promising new antifungal compound and open new opportunities for the future development of novel therapies.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31456952

RESUMO

Cryptococcosis, caused by the basidiomycete Cryptococcus neoformans, is a life-threatening disease affecting approximately one million people per year worldwide. Infection can occur when C. neoformans cells are inhaled by immunocompromised people. In order to establish infection, the yeast must bypass recognition and clearance by immune cells guarding the tissue. Using in vitro infections, we characterized the role of mast cells (MCs) in cryptococcosis. We found that MCs recognize C. neoformans and release inflammatory mediators such as tryptase and cytokines. From the latter group MCs released mainly CCL-2/MCP-1, a strong chemoattractant for monocytic cells. We demonstrated that supernatants of infected MCs recruit monocytes but not neutrophils. During infection with C. neoformans, MCs have a limited ability to kill the yeast depending on the serotype. C. neoformans, in turn, modulates the lifespan of MCs both, by presence of its polysaccharide capsule and by secreting soluble modulators. Taken together, MCs might have important contributions to fungal clearance during early stages of cryptocococis where these cells regulate recruitment of monocytes to mucosal tissues.


Assuntos
Quimiocina CCL2/biossíntese , Criptococose/metabolismo , Criptococose/microbiologia , Cryptococcus neoformans/fisiologia , Interações Hospedeiro-Patógeno , Mastócitos/metabolismo , Mastócitos/microbiologia , Morte Celular , Degranulação Celular/imunologia , Quimiotaxia de Leucócito/imunologia , Criptococose/imunologia , Citocinas/metabolismo , Humanos , Mastócitos/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/microbiologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fagocitose
16.
Semin Cell Dev Biol ; 89: 47-57, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29601861

RESUMO

Fungal infections are a continuously increasing problem in modern health care. Understanding the complex biology of the emerging pathogens and unraveling the mechanisms of host defense may form the basis for the development of more efficient diagnostic and therapeutic tools. Neutrophils play a pivotal role in the defense against fungal pathogens. These phagocytic hunters migrate towards invading fungal microorganisms and eradicate them by phagocytosis, oxidative burst and release of neutrophil extracellular traps (NETs). In the last decade, the process of NET formation has received unparalleled attention, with numerous studies revealing the relevance of this neutrophil function for control of various mycoses. Here, we describe NET formation and summarize its role as part of the innate immune defense against fungal pathogens. We highlight factors influencing the formation of these structures and molecular mechanisms employed by fungi to impair the formation of NETs or subvert their antifungal effects.


Assuntos
Armadilhas Extracelulares/imunologia , Micoses/imunologia , Neutrófilos/imunologia , Fagocitose/imunologia , Antifúngicos/uso terapêutico , Armadilhas Extracelulares/microbiologia , Fungos/imunologia , Fungos/patogenicidade , Humanos , Micoses/microbiologia , Neutrófilos/microbiologia , Espécies Reativas de Oxigênio/imunologia
17.
Br J Cancer ; 120(2): 207-217, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30518816

RESUMO

BACKGROUND: Advanced cancer causes necrosis and releases damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs activate neutrophils, including generation of neutrophil extracellular traps (NETs), which are injurious, thrombogenic, and implicated in metastasis. We hypothesised that extracellular mitochondrial DNA (mtDNA) in ascites from patients with epithelial ovarian cancer (EOC) would correlate with worse outcomes. METHODS: Banked ascites supernatants from patients with newly diagnosed advanced EOC were analysed for mtDNA, neutrophil elastase, and activation of healthy donor neutrophils and platelets. TCGA was mined for expression of SELP and ELANE. RESULTS: The highest quartile of ascites mtDNA correlated with reduced progression-free survival (PFS) and a higher likelihood of disease progression within 12-months following primary surgery (n = 68, log-rank, p = 0.0178). NETs were detected in resected tumours. Ascites supernatants chemoattracted neutrophils, induced NETs, and activated platelets. Ascites exposure rendered neutrophils suppressive, based on abrogation of ex vivo stimulated T cell proliferation. Increased SELP mRNA expression correlated with worse overall survival (n = 302, Cox model, p = 0.02). CONCLUSION: In this single-centre retrospective analysis, ascites mtDNA correlated with worse PFS in advanced EOC. Mitochondrial and other DAMPs in ascites may activate neutrophil and platelet responses that facilitate metastasis and obstruct anti-tumour immunity. These pathways are potential prognostic markers and therapeutic targets.


Assuntos
Alarminas/genética , Carcinoma Epitelial do Ovário/genética , DNA Mitocondrial/genética , Armadilhas Extracelulares/genética , Idoso , Ascite/genética , Ascite/patologia , Plaquetas/metabolismo , Carcinoma Epitelial do Ovário/patologia , Armadilhas Extracelulares/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Elastase de Leucócito/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neutrófilos/metabolismo , Neutrófilos/patologia , Intervalo Livre de Progressão , Microambiente Tumoral/genética
18.
Bio Protoc ; 9(15): e3326, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-33654833

RESUMO

Candida albicans is a leading human fungal pathogen that uses several metabolic adaptations to escape immune cells and causes systemic disease. Here, we describe a protocol for measuring one of these adaptations, the ability to thrive in hypoxic niches. Hypoxia was generated after successful subdermal infection with C. albicans in a murine infection model. Hypoxia was measured using a fluorescent dye for carbonic anhydrase 9, a host enzyme active under hypoxic conditions. Emitted fluorescence was subsequently quantified using an IVIS system. This protocol was optimized for the use in subdermal infection in mice but has the potential to be adapted to other models of fungal infection.

19.
mBio ; 9(6)2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30401781

RESUMO

Microbial colonizers of humans have evolved to adapt to environmental cues and to sense nutrient availability. Oxygen is a constantly changing environmental parameter in different host tissues and in different types of infection. We describe how Candida albicans, an opportunistic fungal pathogen, can modulate the host response under hypoxia and anoxia. We found that high infiltration of polymorphonuclear leukocytes (PMNs) to the site of infection contributes to a low oxygen milieu in a murine subdermal abscess. A persistent hypoxic environment did not affect viability or metabolism of PMNs. Under oxygen deprivation, however, infection with C. albicans disturbed specific PMN responses. PMNs were not able to efficiently phagocytose, produce ROS, or release extracellular DNA traps. Failure to launch an adequate response was caused by C. albicans cell wall masking of ß-glucan upon exposure to low oxygen levels which hindered PAMP sensing by Dectin-1 on the surfaces of PMNs. This in turn contributed to immune evasion and enhanced fungal survival. The cell wall masking effect is prolonged by the accumulation of lactate produced by PMNs under low oxygen conditions. Finally, adaptation to oxygen deprivation increased virulence of C. albicans which we demonstrated using a Caenorhabditis elegans infection model.IMPORTANCE Successful human colonizers have evolved mechanisms to bypass immune surveillance. Infiltration of PMNs to the site of infection led to the generation of a low oxygen niche. Exposure to low oxygen levels induced fungal cell wall masking, which in turn hindered pathogen sensing and antifungal responses by PMNs. The cell wall masking effect was prolonged by increasing lactate amounts produced by neutrophil metabolism under oxygen deprivation. In an invertebrate infection model, C. albicans was able to kill infected C. elegans nematodes within 2 days under low oxygen conditions, whereas the majority of uninfected controls and infected worms under normoxic conditions survived. These results suggest that C. albicans benefited from low oxygen niches to increase virulence. The interplay of C. albicans with innate immune cells under these conditions contributed to the overall outcome of infection. Adaption to low oxygen levels was in addition beneficial for C. albicans by reducing susceptibility to selected antifungal drugs. Hence, immunomodulation of host cells under low oxygen conditions could provide a valuable approach to improve current antifungal therapies.


Assuntos
Candida albicans/imunologia , Candida albicans/patogenicidade , Evasão da Resposta Imune , Oxigênio/metabolismo , Anaerobiose , Animais , Parede Celular/metabolismo , Armadilhas Extracelulares/microbiologia , Feminino , Humanos , Lectinas Tipo C/metabolismo , Camundongos , Infiltração de Neutrófilos , Neutrófilos/imunologia , Neutrófilos/microbiologia , Fagocitose , Pele/microbiologia , Pele/patologia , Virulência , beta-Glucanas/metabolismo
20.
Front Immunol ; 9: 1968, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30254629

RESUMO

Neutrophils are crucial for the human innate immunity and constitute the majority of leukocytes in circulation. Thus, blood neutrophil counts serve as a measure for the immune system's functionality. Hematological patients often have low neutrophil counts due to disease or chemotherapy. To increase neutrophil counts and thereby preventing infections in high-risk patients, recombinant G-CSF is widely used as adjunct therapy to stimulate the maturation of neutrophils. In addition, G-CSF is utilized to recruit stem cells (SCs) into the peripheral blood of SC donors. Still, the actual functionality of neutrophils resulting from G-CSF treatment remains insufficiently understood. We tested the ex vivo functionality of neutrophils isolated from blood of G-CSF-treated healthy SC donors. We quantified chemotaxis, oxidative burst, and phagocytosis before and after treatment and detected significantly reduced chemotactic activity upon G-CSF treatment. Similarly, in vitro treatment of previously untreated neutrophils with G-CSF led to reduced chemotactic activity. In addition, we revealed that this effect persists in the allogeneic SC recipients up to 4 weeks after neutrophil engraftment. Our data indicates that neutrophil quantity, as a sole measure of immunocompetence in high-risk patients should be considered cautiously as neutrophil functionality might be affected by the primary treatment.


Assuntos
Quimiotaxia/efeitos dos fármacos , Filgrastim/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Neutrófilos/metabolismo , Doadores de Tecidos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fagocitose/efeitos dos fármacos , Explosão Respiratória/efeitos dos fármacos
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