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1.
Pak J Biol Sci ; 24(9): 920-927, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34585544

RESUMO

<b>Background and Objective:</b> COVID-19 is a fast-spreading worldwide pandemic caused by SARS-CoV-2. The World Health Organization recommended wearing face masks. Masks have become an urgent necessity throughout the pandemic, the study's goal was to track the impact of wearing masks on immunological responses. <b>Materials and Methods:</b> This study was conducted on 40 healthy people who were working in health care at Nineveh Governorate Hospitals from September-December, 2020. They wore face masks at work for more than 8 months for an average of 6 hrs a day. The control sample included 40 healthy individuals, who wore masks for very short periods. All samples underwent immunological and physiological tests to research the effects of wearing masks for extended periods within these parameters. <b>Results:</b> The results showed a significant decrease in total White Blood Count and the absolute number of neutrophils, lymphocytes, monocytes and phagocytic activity. However, there was a significant increase in the absolute number of eosinophils in participants compared with the control. The results also suggested there were no significant differences in IgE, haemoglobin concentration and blood O<sub>2 </sub>saturation in participants who wore masks for more than 6 hrs compared to the control group. The results showed a significant increase in pulse rate in participants who wore masks for more than 6 hrs compared to the control group. The results also showed a strong correlation coefficient between the time of wearing masks and some immunological, haematological parameters. <b>Conclusion:</b> Wearing masks for long periods alters immunological parameters that initiate the immune response, making the body weaker in its resistance to infectious agents.


Assuntos
COVID-19/prevenção & controle , Exposição por Inalação/prevenção & controle , Leucócitos/imunologia , Máscaras , Exposição Ocupacional/prevenção & controle , Fagócitos/imunologia , SARS-CoV-2/patogenicidade , Adulto , Biomarcadores/sangue , COVID-19/transmissão , Estudos de Casos e Controles , Feminino , Frequência Cardíaca , Hemoglobinas/metabolismo , Humanos , Imunoglobulina E/sangue , Exposição por Inalação/efeitos adversos , Contagem de Leucócitos , Masculino , Máscaras/efeitos adversos , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Oxigênio/sangue , Recursos Humanos em Hospital , Fagocitose , Fatores de Tempo
2.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34518373

RESUMO

Dendritic cells (DC), macrophages, and monocytes, collectively known as mononuclear phagocytes (MPs), critically control tissue homeostasis and immune defense. However, there is a paucity of models allowing to selectively manipulate subsets of these cells in specific tissues. The steady-state adult kidney contains four MP subsets with Clec9a-expression history that include the main conventional DC1 (cDC1) and cDC2 subtypes as well as two subsets marked by CD64 but varying levels of F4/80. How each of these MP subsets contributes to the different phases of acute kidney injury and repair is unknown. We created a mouse model with a Cre-inducible lox-STOP-lox-diphtheria toxin receptor cassette under control of the endogenous CD64 locus that allows for diphtheria toxin-mediated depletion of CD64-expressing MPs without affecting cDC1, cDC2, or other leukocytes in the kidney. Combined with specific depletion of cDC1 and cDC2, we revisited the role of MPs in cisplatin-induced kidney injury. We found that the intrinsic potency reported for CD11c+ cells to limit cisplatin toxicity is specifically attributed to CD64+ MPs, while cDC1 and cDC2 were dispensable. Thus, we report a mouse model allowing for selective depletion of a specific subset of renal MPs. Our findings in cisplatin-induced injury underscore the value of dissecting the functions of individual MP subsets in kidney disease, which may enable therapeutic targeting of specific immune components in the absence of general immunosuppression.


Assuntos
Injúria Renal Aguda/prevenção & controle , Células Dendríticas/imunologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Macrófagos/imunologia , Monócitos/imunologia , Fagócitos/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Feminino , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/metabolismo , Monócitos/patologia , Fagócitos/citologia , Receptores de IgG
3.
Nat Immunol ; 22(10): 1210-1217, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34545250

RESUMO

When helper T (TH) cell polarization was initially described three decades ago, the TH cell universe grew dramatically. New subsets were described based on their expression of few specific cytokines. Beyond TH1 and TH2 cells, this led to the coining of various TH17 and regulatory (Treg) cell subsets as well as TH22, TH25, follicular helper (TFH), TH3, TH5 and TH9 cells. High-dimensional single-cell analysis revealed that a categorization of TH cells into a single-cytokine-based nomenclature fails to capture the complexity and diversity of TH cells. Similar to the simple nomenclature used to describe innate lymphoid cells (ILCs), we propose that TH cell polarization should be categorized in terms of the help they provide to phagocytes (type 1), to B cells, eosinophils and mast cells (type 2) and to non-immune tissue cells, including the stroma and epithelium (type 3). Studying TH cells based on their helper function and the cells they help, rather than phenotypic features such as individual analyzed cytokines or transcription factors, better captures TH cell plasticity and conversion as well as the breadth of immune responses in vivo.


Assuntos
Citocinas/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Linfócitos B/imunologia , Plasticidade Celular/imunologia , Eosinófilos/imunologia , Epitélio/imunologia , Humanos , Imunidade Inata/imunologia , Linfócitos/imunologia , Fagócitos/imunologia
4.
Nat Commun ; 12(1): 4999, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404769

RESUMO

The type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. Ifitm3-/- mice are resistant to systemic infection by Lm, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.


Assuntos
Antibacterianos/farmacologia , Listeria/efeitos dos fármacos , Listeriose/imunologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Fagócitos/imunologia , Fagócitos/microbiologia , Animais , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno , Interferon Tipo I/metabolismo , Listeria monocytogenes/imunologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fagossomos/imunologia , Células RAW 264.7 , Transcriptoma , Fatores de Virulência , Internalização do Vírus/efeitos dos fármacos
5.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445642

RESUMO

Endocytosis provides the cellular nutrition and homeostasis of organisms, but pathogens often take advantage of this entry point to infect host cells. This is counteracted by phagocytosis that plays a key role in the protection against invading microbes both during the initial engulfment of pathogens and in the clearance of infected cells. Phagocytic cells balance two vital functions: preventing the accumulation of cell corpses to avoid pathological inflammation and autoimmunity, whilst maintaining host defence. In this review, we compare elements of phagocytosis in mammals and the nematode Caenorhabditis elegans. Initial recognition of infection requires different mechanisms. In mammals, pattern recognition receptors bind pathogens directly, whereas activation of the innate immune response in the nematode rather relies on the detection of cellular damage. In contrast, molecules involved in efferocytosis-the engulfment and elimination of dying cells and cell debris-are highly conserved between the two species. Therefore, C. elegans is a powerful model to research mechanisms of the phagocytic machinery. Finally, we show that both mammalian and worm studies help to understand how the two phagocytic functions are interconnected: emerging data suggest the activation of innate immunity as a consequence of defective apoptotic cell clearance.


Assuntos
Apoptose , Imunidade Inata/imunologia , Fagócitos/fisiologia , Fagocitose , Animais , Caenorhabditis elegans , Humanos , Transdução de Sinais
6.
Clin Immunol ; 229: 108796, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34271191

RESUMO

INTRODUCTION: Inherited phagocyte defects are one of the subgroups of primary immunodeficiency diseases (PIDs) with various clinical manifestations. As oral manifestations are common at the early ages, oral practitioners can have a special role in the early diagnosis. MATERIALS AND METHODS: A comprehensive search was conducted in this systematic review study and data of included studies were categorized into four subgroups of phagocyte defects, including congenital neutropenia, defects of motility, defects of respiratory burst, and other non-lymphoid defects. RESULTS: Among all phagocyte defects, 12 disorders had reported data for oral manifestations in published articles. A total of 987 cases were included in this study. Periodontitis is one of the most common oral manifestations. CONCLUSION: There is a need to organize better collaboration between medical doctors and dentists to diagnose and treat patients with phagocyte defects. Regular dental visits and professional oral health care are recommended from the time of the first primary teeth eruption in newborns.


Assuntos
Doenças da Boca/imunologia , Fagócitos/imunologia , Doenças da Imunodeficiência Primária/imunologia , Feminino , Deficiência de GATA2/diagnóstico , Deficiência de GATA2/genética , Deficiência de GATA2/imunologia , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/imunologia , Humanos , Masculino , Doenças da Boca/diagnóstico , Doenças da Boca/genética , Neutropenia/congênito , Neutropenia/diagnóstico , Neutropenia/imunologia , Doença de Papillon-Lefevre/diagnóstico , Doença de Papillon-Lefevre/genética , Doença de Papillon-Lefevre/imunologia , Fagócitos/patologia , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/genética , Explosão Respiratória/genética , Explosão Respiratória/imunologia
7.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206148

RESUMO

Sea urchins are long-living marine invertebrates with a complex innate immune system, which includes expanded families of immune receptors. A central immune gene family in sea urchins encodes the Transformer (Trf) proteins. The Trf family has been studied mainly in the purple sea urchin Strongylocentrotus purpuratus. Here, we explore this protein family in the Mediterranean Sea urchin Paracentrotus lividus. The PlTrf genes and predicted proteins are highly diverse and show a typical Trf size range and structure. Coelomocytes and cell-free coelomic fluid from P. lividus contain different PlTrf protein repertoires with a shared subset, that bind specifically to E. coli. Using FACS, we identified five different P. lividus coelomocyte sub-populations with cell surface PlTrf protein expression. The relative abundance of the PlTrf-positive cells increases sharply following immune challenge with E. coli, but not following challenge with LPS or the sea urchin pathogen, Vibrio penaeicida. Phagocytosis of E. coli by P. lividus phagocytes is mediated through the cell-free coelomic fluid and is inhibited by blocking PlTrf activity with anti-SpTrf antibodies. Together, our results suggest a collaboration between cellular and humoral PlTrf-mediated effector arms in the P. lividus specific immune response to pathogens.


Assuntos
Imunidade Celular , Imunidade Humoral , Paracentrotus/imunologia , Fagocitose , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/imunologia , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/metabolismo , Sequência de Aminoácidos , Animais , Escherichia coli , Evolução Molecular , Paracentrotus/genética , Paracentrotus/microbiologia , Fagócitos/imunologia , Fagócitos/metabolismo , Fagócitos/microbiologia , Filogenia , Conformação Proteica , Elementos Estruturais de Proteínas , Alinhamento de Sequência , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/química , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/genética , Vibrio
9.
Methods Mol Biol ; 2314: 649-702, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235675

RESUMO

Mycobacterium tuberculosis is able to colonize, persist, and massively replicate in host cells, such as phagocytes and epithelial cells. The intracellular stage of the bacteria is critical to the development of tuberculosis pathogenesis. The detailed mechanisms of intracellular trafficking of the bacillus are not fully understood and require further investigations. Therefore, increasing the knowledge of this process will help to develop therapeutic tools that will lower the burden of tuberculosis. M. tuberculosis is genetically tractable and tolerates the expression of heterologous fluorescent proteins. Thus, the intracellular distribution of the bacteria expressing fluorescent tracers can be easily defined using confocal microscopy. Advances in imaging techniques and images-based analysis allow the rapid quantification of biological objects in complex environments. In this chapter, we detailed high-content / high-throughput imaging methods to track the bacillus within host cell settings.


Assuntos
Células Dendríticas/microbiologia , Células Epiteliais/microbiologia , Ensaios de Triagem em Larga Escala/métodos , Macrófagos/microbiologia , Mycobacterium tuberculosis/crescimento & desenvolvimento , Fagócitos/microbiologia , Tuberculose/microbiologia , Animais , Células Dendríticas/metabolismo , Testes Diagnósticos de Rotina , Células Epiteliais/metabolismo , Humanos , Macrófagos/metabolismo , Camundongos , Mycobacterium tuberculosis/patogenicidade , Estresse Oxidativo , Fagócitos/metabolismo , Espécies Reativas de Oxigênio , Tuberculose/metabolismo
10.
Am J Physiol Lung Cell Mol Physiol ; 321(3): L566-L575, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34287085

RESUMO

The influence of smoke-derived or air pollution-derived cytoplasmic particulate matter (PM) can be detrimental and can lead to failed lung immunity. We investigated mycobacterial uptake, intracellular replication, and soluble immune-mediator responses of human bronchoalveolar lavage cells (BALCs) loaded with/without PM, to infection with mycobacterial strains. We observed that only BALCs containing PM display an ex vivo phenotypic profile dominated by spontaneous interleukin (IL)-10 production. PM-loaded BALCs retained the ability to phagocytose both Mycobacterium bovis Bacille Calmette Guérin (BCG) and Mycobacterium tuberculosis (M.tb) ΔleuDΔpanCD at equal efficacy as clear non-PM-loaded BALCs. However, immune responsiveness, such as the production of IL-6 (P = 0.015) and tumor necrosis factor-α (TNF)-α (P = 0.0172) immediately post M. bovis BCG infection, were dramatically lower in black BALCs loaded with PM versus clear non-PM-loaded BALCs. By 24 h post infection, differential immune responses to M. bovis BCG between black versus clear BALC waned, and instead, production of IL-6 (P = 0.03) and IL-1α (P = 0.04) by black BALCs was lower versus clear BALCs following M.tb ΔleuDΔpanCD infection. Considering that TNF-α and IL-6 are characterized as critical to host protection against mycobacteria, our findings suggest that BALCs loaded with inhaled PM, display lower levels of antimycobacterial mediators and that the response magnitude differs according to infective mycobacterial strain. Even though this did not translate into altered mycobacterial killing at early time points post infection, the long-term impact of such changes remains to be established.


Assuntos
Exposição por Inalação/efeitos adversos , Pulmão/imunologia , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/imunologia , Material Particulado/efeitos adversos , Fagócitos/imunologia , Líquido da Lavagem Broncoalveolar , Feminino , Humanos , Pulmão/microbiologia , Pulmão/patologia , Masculino , Monocinas/imunologia , Fagócitos/microbiologia , Fagócitos/patologia
11.
Exp Eye Res ; 210: 108692, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34228965

RESUMO

Fuchs' endothelial corneal dystrophy (FECD) is a progressive vision impairing disease caused by thickening of Descemet's membrane and gradual degeneration and loss of corneal endothelial cells. The aim of this study was to identify differentially expressed genes between FECD-affected and unaffected corneal endothelium to gain insight into the pathophysiological mechanisms underlying this disease. Microarray gene expression analysis was performed on total RNA from FECD-affected and unaffected corneal endothelium-Descemet's membrane (CE-DM) specimens using the Illumina HumanHT-12 v4.0 expression array. RNA from pools of FECD-affected (n = 3 per pool) and individual unaffected (n = 3) specimens was used for comparison. Altered expression of a sub-set of differentially expressed genes was validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in independent specimens. Bioinformatics analysis was performed using InnateDB to reveal functional relationships among the differentially expressed genes and molecular pathways involved in the disease. A total of 16,513 genes were found expressed in the corneal endothelium of which 142 genes were differentially expressed between FECD-affected and unaffected endothelium (log2 fold-change ≥1.5, corrected p-value ≤0.05). Most of the genes were up-regulated (126) and a small proportion down-regulated (16) in affected corneal endothelium. Of the twelve genes prioritised for validation, differential expression of 10 genes, including those ranked 57th and 81st by significance validated by qRT-PCR (8 up-regulated and 2 downregulated, corrected p ≤ 0.05), one gene showed a trend for up-regulation in affected endothelium, consistent with the microarray analysis and another was up-regulated in an independent study indicating robustness of the differential expression dataset. Bioinformatic analysis revealed significant over-representation of differentially expressed genes in extracellular matrix reorganisation, cellular remodelling, immune response, and inflammation. Network analysis showed functional inter-relatedness of the majority of the dysregulated genes and revealed known direct functional relationships between 20 of the genes; many of these genes have roles in macrophage differentiation, phagocytosis and inflammation. This is the second report of microarray gene expression analysis in FECD. This study revealed a set of highly dysregulated genes in the corneal endothelium in FECD. More than a third of the dysregulated genes in the disease have been discovered for the first time and thus are novel. The dysregulated genes strongly suggest the presence of phagocytic cells, most likely immune cells, and inflammation in corneal endothelium in the disease. This study provides a molecular framework for delineating the mechanisms underlying these cellular processes in FECD.


Assuntos
Endotélio Corneano/metabolismo , Proteínas do Olho/genética , Distrofia Endotelial de Fuchs/genética , Regulação da Expressão Gênica/fisiologia , Fagócitos/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Feminino , Distrofia Endotelial de Fuchs/fisiopatologia , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise Serial de Proteínas , RNA/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real
12.
Am J Pathol ; 191(10): 1787-1804, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34197777

RESUMO

Although pathologies associated with acute virus infections have been extensively studied, the effects of long-term latent virus infections are less well understood. Human cytomegalovirus, which infects 50% to 80% of humans, is usually acquired during early life and persists in a latent state for the lifetime. The purpose of this study was to determine whether systemic murine cytomegalovirus (MCMV) infection acquired early in life disseminates to and becomes latent in the eye and if ocular MCMV can trigger in situ inflammation and occurrence of ocular pathology. This study found that neonatal infection of BALB/c mice with MCMV resulted in dissemination of virus to the eye, where it localized principally to choroidal endothelia and pericytes and less frequently to the retinal pigment epithelium (RPE) cells. MCMV underwent ocular latency, which was associated with expression of multiple virus genes and from which MCMV could be reactivated by immunosuppression. Latent ocular infection was associated with significant up-regulation of several inflammatory/angiogenic factors. Retinal and choroidal pathologies developed in a progressive manner, with deposits appearing at both basal and apical aspects of the RPE, RPE/choroidal atrophy, photoreceptor degeneration, and neovascularization. The pathologies induced by long-term ocular MCMV latency share features of previously described human ocular diseases, such as age-related macular degeneration.


Assuntos
Envelhecimento/patologia , Corioide/patologia , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Muromegalovirus/fisiologia , Retina/patologia , Indutores da Angiogênese/metabolismo , Animais , Animais Recém-Nascidos , Antígenos Virais/metabolismo , Corioide/diagnóstico por imagem , Corioide/ultraestrutura , Corioide/virologia , DNA Viral/metabolismo , Regulação Viral da Expressão Gênica , Infecções por Herpesviridae/diagnóstico por imagem , Interações Hospedeiro-Patógeno , Imunossupressão , Inflamação/patologia , Camundongos Endogâmicos BALB C , Muromegalovirus/genética , Fagócitos/patologia , Retina/diagnóstico por imagem , Retina/ultraestrutura , Retina/virologia , Epitélio Pigmentado da Retina/diagnóstico por imagem , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica , Ativação Viral
13.
Biosens Bioelectron ; 191: 113412, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34153636

RESUMO

Phagocytic cells recognize and phagocytose invading microbes for destruction. However, bacterial pathogens can remain hidden at low levels from conventional detection or replicate intracellularly after being phagocytosed by immune cells. Current phagocytosis-detection approaches involve flow cytometry or microscopic search for rare bacteria-internalized phagocytes among large populations of uninfected cells, which poses significant challenges in research and clinical settings. Hence it is imperative to develop a rapid, non-disruptive, and label-free phagocytosis detection approach. Using deformability assays and microscopic imaging, we have demonstrated for the first time that the presence of intracellular bacteria in phagocytic blood cells led to aberrant physical properties. Specifically, human monocytes with internalized bacteria of various species were stiffer and larger compared with uninfected monocytes. Taking advantage of these physical differences, a novel microfluidics-based biosensor platform was developed to passively sort, concentrate and quantify rare monocytes with internalized pathogens (MIP) from uninfected monocyte populations for phagocytosis detection. The clinical utility of the MIP platform was demonstrated by enriching and detecting bacteria-internalized monocytes from spiked human blood samples within 1.5 h. Patient-derived clinical isolates were used to validate the utility of the MIP platform further. This proof-of-concept presents a phagocytosis detection platform that could be used to rapidly diagnose microbial infections, especially in bloodstream infections (BSIs), thereby improving the clinical outcomes for point-of-care management.


Assuntos
Infecções Bacterianas , Técnicas Biossensoriais , Infecções Bacterianas/diagnóstico , Humanos , Monócitos , Fagócitos , Fagocitose
14.
Front Immunol ; 12: 645168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093534

RESUMO

Accumulating evidence indicates that nutrition can modulate the immune system through metabolites, either produced by host digestion or by microbiota metabolism. In this review, we focus on dietary metabolites that are agonists of the Aryl hydrocarbon Receptor (AhR). AhR is a ligand-activated transcription factor, initially characterized for its interaction with xenobiotic pollutants. Numerous studies have shown that AhR also recognizes indoles and tryptophan catabolites originating from dietary compounds and commensal bacteria. Here, we review recent work employing diet manipulation to address the impact of nutritional AhR agonists on immune responses, both locally in the intestine and at distant sites. In particular, we examine the physiological role of these metabolites in immune cell development and functions (including T lymphocytes, innate-like lymphoid cells, and mononuclear phagocytes) and their effect in inflammatory disorders.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Alimentos , Intestinos/imunologia , Fagócitos/imunologia , Receptores de Hidrocarboneto Arílico/imunologia , Linfócitos T/imunologia , Humanos , Inflamação/imunologia , Ligantes
15.
Front Immunol ; 12: 657344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084165

RESUMO

Modified or misplaced DNA can be recognized as a danger signal by mammalian cells. Activation of cellular responses to DNA has evolved as a defense mechanism to microbial infections, cellular stress, and tissue damage, yet failure to control this mechanism can lead to autoimmune diseases. Several monogenic and multifactorial autoimmune diseases have been associated with type-I interferons and interferon-stimulated genes (ISGs) induced by deregulated recognition of self-DNA. Hence, understanding how cellular mechanism controls the pathogenic responses to self-nucleic acid has important clinical implications. Fine-tuned membrane trafficking and cellular compartmentalization are two major factors that balance activation of DNA sensors and availability of self-DNA ligands. Intracellular transport and organelle architecture are in turn regulated by cytoskeletal dynamics, yet the precise impact of actin remodeling on DNA sensing remains elusive. This review proposes a critical analysis of the established and hypothetical connections between self-DNA recognition and actin dynamics. As a paradigm of this concept, we discuss recent evidence of deregulated self-DNA sensing in the prototypical actin-related primary immune deficiency (Wiskott-Aldrich syndrome). We anticipate a broader impact of actin-dependent processes on tolerance to self-DNA in autoimmune disorders.


Assuntos
Autoimunidade , DNA/imunologia , Proteínas de Membrana/metabolismo , Nucleotidiltransferases/metabolismo , Receptor Toll-Like 9/metabolismo , Animais , Doenças Autoimunes/etiologia , Doenças Autoimunes/metabolismo , Citoesqueleto/metabolismo , Endossomos/metabolismo , Humanos , Fagócitos/imunologia , Fagócitos/metabolismo , Ligação Proteica , Transporte Proteico , Transdução de Sinais
16.
Exp Cell Res ; 405(2): 112709, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34174318

RESUMO

We earlier identified native human trabecular meshwork stem cells (TMSCs) based on two-parameters- high ABCG2 expression and high nucleus to cytoplasmic ratio. The TMSCs also expressed p75 and AnkyrinG. Based on the high expression of ABCG2 and p75, the TMSCs were identified to be located in the Schwalbe's line region of the TM. In continuation, the current study aimed at elucidating the functional characteristics of human TMSCs. Upon culturing, only a small proportion of TM cells (0.96 ± 0.21% in <30 years) expressing stem cell markers ABCG2 and p75 adhered to the culture dish. This proportion significantly reduced with ageing (0.32 ± 0.23% in 30-60 years and 0.35 ± 0.04% in >60 years). Characterization of the primary TM cultures identified 7.00 ± 1.80% of stem cells with label retaining property. Further, cultured cells had the ability to form TM spheres (0.82 ± 0.23%) which consisted of high ABCG2 and p75 positive cells. Upon dexamethasone induction, 86.00 ± 14.87% and 64.60 ± 7.24% of the cells derived from the TM spheres expressed myocilin and exhibited cross linked actin networks respectively, indicating differentiation of the TMSCs in the sphere to TM cells. In addition, the sphere derived TM cells also possessed phagocytic potential (13.28 ± 3.30%) equivalent to primary TM cells (16.33 ± 4.04%) which was evident upon internalization of zymosan particles. In conclusion, this study has established that a proportion of cultured TM cells had the label retaining property as well as sphere forming ability of adult stem cells. Thus, these results confirm the presence of adult stem cells in the human TM that might be responsible for the maintenance of tissue homeostasis.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Dexametasona/farmacologia , Células-Tronco/efeitos dos fármacos , Malha Trabecular/efeitos dos fármacos , Adulto , Células-Tronco Adultas/citologia , Células-Tronco Adultas/efeitos dos fármacos , Proteínas do Citoesqueleto/metabolismo , Proteínas do Olho/metabolismo , Glicoproteínas/metabolismo , Homeostase/fisiologia , Humanos , Fagócitos/citologia , Fagócitos/efeitos dos fármacos , Células-Tronco/citologia , Malha Trabecular/metabolismo
17.
Front Immunol ; 12: 660873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093550

RESUMO

Aedes aegypti mosquitoes are vectors for arboviruses of medical importance such as dengue (DENV) and Zika (ZIKV) viruses. Different innate immune pathways contribute to the control of arboviruses in the mosquito vector including RNA interference, Toll and Jak-STAT pathways. However, the role of cellular responses mediated by circulating macrophage-like cells known as hemocytes remains unclear. Here we show that hemocytes are recruited to the midgut of Ae. aegypti mosquitoes in response to DENV or ZIKV. Blockade of the phagocytic function of hemocytes using latex beads induced increased accumulation of hemocytes in the midgut and a reduction in virus infection levels in this organ. In contrast, inhibition of phagocytosis by hemocytes led to increased systemic dissemination and replication of DENV and ZIKV. Hence, our work reveals a dual role for hemocytes in Ae. aegypti mosquitoes, whereby phagocytosis is not required to control viral infection in the midgut but is essential to restrict systemic dissemination. Further understanding of the mechanism behind this duality could help the design of vector-based strategies to prevent transmission of arboviruses.


Assuntos
Aedes/citologia , Aedes/virologia , Vírus da Dengue/fisiologia , Hemócitos/imunologia , Hemócitos/virologia , Zika virus/fisiologia , Aedes/anatomia & histologia , Animais , Feminino , Hemócitos/fisiologia , Mosquitos Vetores , Fagócitos/virologia , Fagocitose
18.
Front Immunol ; 12: 660865, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177900

RESUMO

The resolution of inflammation is a tissue protective program that is governed by several factors including specialized pro-resolving mediators (SPMs), proteins, gasses and nucleotides. Pro-resolving mediators activate counterregulatory programs to quell inflammation and promote tissue repair in a manner that does not compromise host defense. Phagocytes like neutrophils and macrophages play key roles in the resolution of inflammation because of their ability to remove debris, microbes and dead cells through processes including phagocytosis and efferocytosis. Emerging evidence suggests that failed resolution of inflammation and defective phagocytosis or efferocytosis underpins several prevalent human diseases. Therefore, understanding factors and mechanisms associated with enhancing these processes is a critical need. SPMs enhance phagocytosis and efferocytosis and this review will highlight mechanisms associated with their actions.


Assuntos
Inflamação , Ligantes , Fagócitos/imunologia , Fagocitose , Animais , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Neutrófilos/imunologia , Neutrófilos/metabolismo
19.
PLoS Biol ; 19(5): e3001259, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34038417

RESUMO

Removal of apoptotic cells is essential for maintenance of tissue homeostasis. Chemotactic cues termed "find-me" signals attract phagocytes toward apoptotic cells, which selectively expose the anionic phospholipid phosphatidylserine (PS) and other "eat-me" signals to distinguish healthy from apoptotic cells for phagocytosis. Blebs released by apoptotic cells can deliver find-me signals; however, the mechanism is poorly understood. Here, we demonstrate that apoptotic blebs generated in vivo from mouse thymus attract phagocytes using endogenous chemokines bound to the bleb surface. We show that chemokine binding to apoptotic cells is mediated by PS and that high affinity binding of PS and other anionic phospholipids is a general property of many but not all chemokines. Chemokines are positively charged proteins that also bind to anionic glycosaminoglycans (GAGs) on cell surfaces for presentation to leukocyte G protein-coupled receptors (GPCRs). We found that apoptotic cells down-regulate GAGs as they up-regulate PS on the cell surface and that PS-bound chemokines, unlike GAG-bound chemokines, are able to directly activate chemokine receptors. Thus, we conclude that PS-bound chemokines may serve as find-me signals on apoptotic vesicles acting at cognate chemokine receptors on leukocytes.


Assuntos
Apoptose/imunologia , Apoptose/fisiologia , Quimiocinas/metabolismo , Animais , Vesícula/metabolismo , Células CHO , Membrana Celular/metabolismo , Quimiocinas/fisiologia , Quimiotaxia , Cricetulus , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fagócitos/metabolismo , Fagocitose/fisiologia , Fosfatidilserinas/metabolismo , Receptores de Quimiocinas/metabolismo , Transdução de Sinais/fisiologia
20.
J Leukoc Biol ; 110(2): 213-215, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33993516

RESUMO

Discussion on the molecular mechanism of phagocyte NADPH oxidase activation.


Assuntos
NADPH Oxidases , Fosfoproteínas , Humanos , Oxazóis , Fagócitos
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