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1.
Nat Commun ; 12(1): 6193, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702812

RESUMO

Staphylococcus aureus bi-component pore-forming leukocidins are secreted toxins that directly target and lyse immune cells. Intriguingly, one of the leukocidins, Leukocidin AB (LukAB), is found associated with the bacterial cell envelope in addition to secreted into the extracellular milieu. Here, we report that retention of LukAB on the bacterial cells provides S. aureus with a pre-synthesized active toxin that kills immune cells. On the bacteria, LukAB is distributed as discrete foci in two distinct compartments: membrane-proximal and surface-exposed. Through genetic screens, we show that a membrane lipid, lysyl-phosphatidylglycerol (LPG), and lipoteichoic acid (LTA) contribute to LukAB deposition and release. Furthermore, by studying non-covalently surface-bound proteins we discovered that the sorting of additional exoproteins, such as IsaB, Hel, ScaH, and Geh, are also controlled by LPG and LTA. Collectively, our study reveals a multistep secretion system that controls exoprotein storage and protein translocation across the S. aureus cell wall.


Assuntos
Membrana Celular/metabolismo , Parede Celular/metabolismo , Staphylococcus aureus/metabolismo , Fatores de Virulência/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/toxicidade , Citotoxinas/metabolismo , Citotoxinas/toxicidade , Humanos , Leucocidinas/metabolismo , Leucocidinas/toxicidade , Lipopolissacarídeos/genética , Lipopolissacarídeos/metabolismo , Lisina/genética , Lisina/metabolismo , Camundongos , Fagócitos/efeitos dos fármacos , Fosfatidilgliceróis/genética , Fosfatidilgliceróis/metabolismo , Transporte Proteico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Ácidos Teicoicos/genética , Ácidos Teicoicos/metabolismo , Fatores de Virulência/toxicidade
2.
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
3.
Sci Rep ; 11(1): 17958, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504130

RESUMO

Several plant lectins, or carbohydrate-binding proteins, interact with glycan moieties on the surface of immune cells, thereby influencing the immune response of these cells. Orysata, a mannose-binding lectin from rice, has been reported to exert immunomodulatory activities on insect cells. While the natural lectin is non-glycosylated, recombinant Orysata produced in the yeast Pichia pastoris (YOry) is modified with a hyper-mannosylated N-glycan. Since it is unclear whether this glycosylation can affect the YOry activity, non-glycosylated rOrysata was produced in Escherichia coli (BOry). In a comparative analysis, both recombinant Orysata proteins were tested for their carbohydrate specificity on a glycan array, followed by the investigation of the carbohydrate-dependent agglutination of red blood cells (RBCs) and the carbohydrate-independent immune responses in Drosophila melanogaster S2 cells. Although YOry and BOry showed a similar carbohydrate-binding profiles, lower concentration of BOry were sufficient for the agglutination of RBCs and BOry induced stronger immune responses in S2 cells. The data are discussed in relation to different hypotheses explaining the weaker responses of glycosylated YOry. In conclusion, these observations contribute to the understanding how post-translational modification can affect protein function, and provide guidance in the selection of the proper expression system for the recombinant production of lectins.


Assuntos
Drosophila melanogaster/citologia , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Lectinas de Ligação a Manose/metabolismo , Lectinas de Ligação a Manose/farmacologia , Oryza/química , Fagócitos/efeitos dos fármacos , Fagócitos/imunologia , Lectinas de Plantas/metabolismo , Lectinas de Plantas/farmacologia , Polissacarídeos/metabolismo , Animais , Linhagem Celular , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Glicosilação , Hemaglutinação/efeitos dos fármacos , Lectinas de Ligação a Manose/genética , Fagócitos/metabolismo , Lectinas de Plantas/genética , Ligação Proteica , Coelhos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Saccharomycetales/genética , Saccharomycetales/metabolismo
4.
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
5.
Int J Mol Sci ; 22(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34502474

RESUMO

Glycosphingolipids (GSLs), together with cholesterol, sphingomyelin (SM), and glycosylphosphatidylinositol (GPI)-anchored and membrane-associated signal transduction molecules, form GSL-enriched microdomains. These specialized microdomains interact in a cis manner with various immune receptors, affecting immune receptor-mediated signaling. This, in turn, results in the regulation of a broad range of immunological functions, including phagocytosis, cytokine production, antigen presentation and apoptosis. In addition, GSLs alone can regulate immunological functions by acting as ligands for immune receptors, and exogenous GSLs can alter the organization of microdomains and microdomain-associated signaling. Many pathogens, including viruses, bacteria and fungi, enter host cells by binding to GSL-enriched microdomains. Intracellular pathogens survive inside phagocytes by manipulating intracellular microdomain-driven signaling and/or sphingolipid metabolism pathways. This review describes the mechanisms by which GSL-enriched microdomains regulate immune signaling.


Assuntos
Glicoesfingolipídeos/imunologia , Microdomínios da Membrana/imunologia , Fagócitos/imunologia , Transdução de Sinais/imunologia , Animais , Apresentação do Antígeno/imunologia , Apoptose/imunologia , Humanos , Fagocitose/imunologia
6.
Trends Immunol ; 42(10): 904-919, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34503911

RESUMO

Mucosal sites, such as the lung, serve as crucial, yet vulnerable barriers to environmental insults such as pathogens, allergens, and toxins. Often, these exposures induce massive infiltration and death of short-lived immune cells in the lung, and efficient clearance of these cells is important for preventing hyperinflammation and resolving immunopathology. Herein, we review recent advances in our understanding of efferocytosis, a process whereby phagocytes clear dead cells in a noninflammatory manner. We further discuss how efferocytosis impacts the onset and severity of asthma in humans and mammalian animal models of disease. Finally, we explore how recently identified genetic perturbations or biological pathway modulations affect pathogenesis and shed light on novel therapies aimed at treating or preventing asthma.


Assuntos
Asma , Inflamação , Animais , Apoptose , Humanos , Fagócitos , Fagocitose
7.
Trends Immunol ; 42(10): 846-848, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34538594

RESUMO

Selectively targeting facets of neutrophil function could benefit infectious and inflammatory diseases. Amara et al. report on a compound which blocks human neutrophil activation by activating the glycolytic enzyme phosphofructokinase, liver-type (PFKL). Altering glucose fate by modulating this key enzymatic step could dramatically alter the function and fate of phagocytes.


Assuntos
Neutrófilos , Fagócitos , Glucose , Humanos , Ativação de Neutrófilo , Fosfofrutoquinase-1
8.
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
9.
Cells ; 10(9)2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34571885

RESUMO

Classically, the following three morphological states of microglia have been defined: ramified, amoeboid and phagocytic. While ramified cells were long regarded as "resting", amoeboid and phagocytic microglia were viewed as "activated". In aged human brains, a fourth, morphologically novel state has been described, i.e., dystrophic microglia, which are thought to be senescent cells. Since microglia are not replenished by blood-borne mononuclear cells under physiological circumstances, they seem to have an "expiration date" limiting their capacity to phagocytose and support neurons. Identifying factors that drive microglial aging may thus be helpful to delay the onset of neurodegenerative diseases, such as Alzheimer's disease (AD). Recent progress in single-cell deep sequencing methods allowed for more refined differentiation and revealed regional-, age- and sex-dependent differences of the microglial population, and a growing number of studies demonstrate various expression profiles defining microglial subpopulations. Given the heterogeneity of pathologic states in the central nervous system, the need for accurately describing microglial morphology and expression patterns becomes increasingly important. Here, we review commonly used microglial markers and their fluctuations in expression in health and disease, with a focus on IBA1 low/negative microglia, which can be found in individuals with liver disease.


Assuntos
Encéfalo/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas dos Microfilamentos/metabolismo , Microglia/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Doenças Neurodegenerativas/metabolismo , Fagócitos/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos B/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Encéfalo/patologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Microglia/patologia , Doenças Neurodegenerativas/patologia , Fagócitos/patologia , Fenótipo , Receptores Purinérgicos P2Y12/metabolismo , Transdução de Sinais
10.
PLoS One ; 16(9): e0257792, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34559852

RESUMO

Spray-dried animal plasma (SDP) in feed for several animal species provides health benefits, but research about use of SDP in shrimp feed is very limited. The objectives of the present study were to investigate the effects of dietary SDP on growth performance, feed utilization, immune responses, and prevention of Vibrio parahaemolyticus infection in Pacific white shrimp (Litopenaeus vannamei). In Experiment 1, the post-larvae were divided into five groups (four tank/group and 80 shrimp/tank) and fed four times daily diets with porcine SDP at 0, 1.5, 3, 4.5, and 6% of the diet for 45 days. In Experiment 2, the surviving shrimp from Experiment 1 were redistributed into six groups: four SDP groups as in Experiment 1 plus the positive and negative controls (four tank/group and 30 shrimp/tank). They were then challenged with V. parahaemolyticus by immersion at 105 colony-forming units (CFU)/mL and were fed with the same diets for another 4 days. In Experiment 1, shrimp fed 4.5% or 6% SDP diets had significantly higher body weight, survival rate, and improved feed conversion ratio. The immune parameters (total hemocyte count and phagocytic, phenoloxidase, and superoxide dismutase activities) of the shrimp fed 3-6% SDP diets also showed significant enhancement compared to the control. In Experiment 2, the survival rates of the 3-6% SDP groups were significantly higher than the positive control at day 4 after the immersion challenge. Likewise, the histopathological study revealed milder signs of bacterial infection in the hepatopancreas of the 3-6% SDP groups compared to the challenged positive control and 1.5% SDP groups. In conclusion, shrimp fed diets with SDP, especially at 4.5-6% of the diet, showed significant improvement in overall health conditions and better resistance to V. parahaemolyticus infection.


Assuntos
Suplementos Nutricionais/análise , Resistência à Doença , Penaeidae/crescimento & desenvolvimento , Plasma/química , Vibrio parahaemolyticus/imunologia , Ração Animal/análise , Animais , Peso Corporal , Hemócitos/metabolismo , Imunidade Inata , Larva/crescimento & desenvolvimento , Larva/imunologia , Larva/virologia , Penaeidae/imunologia , Penaeidae/virologia , Fagócitos/metabolismo , Secagem por Atomização , Suínos
11.
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
12.
EMBO Rep ; 22(9): e52262, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34370384

RESUMO

Programmed cell death plays a fundamental role in development and tissue homeostasis. Professional and non-professional phagocytes achieve the proper recognition, uptake, and degradation of apoptotic cells, a process called efferocytosis. Failure in efferocytosis leads to autoimmune and neurodegenerative diseases. In Drosophila, two transmembrane proteins of the Nimrod family, Draper and SIMU, mediate the recognition and internalization of apoptotic corpses. Beyond this early step, little is known about how apoptotic cell degradation is regulated. Here, we study the function of a secreted member of the Nimrod family, NimB4, and reveal its crucial role in the clearance of apoptotic cells. We show that NimB4 is expressed by macrophages and glial cells, the two main types of phagocytes in Drosophila. Similar to draper mutants, NimB4 mutants accumulate apoptotic corpses during embryogenesis and in the larval brain. Our study points to the role of NimB4 in phagosome maturation, more specifically in the fusion between the phagosome and lysosomes. We propose that similar to bridging molecules, NimB4 binds to apoptotic corpses to engage a phagosome maturation program dedicated to efferocytosis.


Assuntos
Drosophila , Fagócitos , Animais , Apoptose/genética , Cadáver , Drosophila/genética , Fagocitose , Fagossomos
13.
Front Immunol ; 12: 662803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381444

RESUMO

Phagocytosis is the cellular defense mechanism used to eliminate antigens derived from dysregulated or damaged cells, and microbial pathogens. Phagocytosis is therefore a pillar of innate immunity, whereby foreign particles are engulfed and degraded in lysolitic vesicles. In hexacorallians, phagocytic mechanisms are poorly understood, though putative anthozoan phagocytic cells (amoebocytes) have been identified histologically. We identify and characterize phagocytes from the coral Pocillopora damicornis and the sea anemone Nematostella vectensis. Using fluorescence-activated cell sorting and microscopy, we show that distinct populations of phagocytic cells engulf bacteria, fungal antigens, and beads. In addition to pathogenic antigens, we show that phagocytic cells engulf self, damaged cells. We show that target antigens localize to low pH phagolysosomes, and that degradation is occurring within them. Inhibiting actin filament rearrangement interferes with efficient particle phagocytosis but does not affect small molecule pinocytosis. We also demonstrate that cellular markers for lysolitic vesicles and reactive oxygen species (ROS) correlate with hexacorallian phagocytes. These results establish a foundation for improving our understanding of hexacorallian immune cell biology.


Assuntos
Antozoários/imunologia , Fagócitos/imunologia , Animais , Antozoários/metabolismo , Biomarcadores , Citocinas/metabolismo , Vesículas Citoplasmáticas/metabolismo , Citometria de Fluxo , Concentração de Íons de Hidrogênio , Imunidade Inata , Fagócitos/citologia , Fagócitos/metabolismo , Fagocitose/imunologia , Fagossomos , Anêmonas-do-Mar
14.
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
15.
Cells ; 10(8)2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34440622

RESUMO

The immune system has evolved to protect organisms from infections caused by bacteria, viruses, and parasitic pathogens. In addition, it provides regenerative capacities, tissue maintenance, and self/non-self recognition of foreign tissues. Phagocytosis and cytotoxicity are two prominent cellular immune activities positioned at the base of immune effector function in mammals. Although these immune mechanisms have diversified into a wide heterogeneous repertoire of effector cells, it appears that they share some common cellular and molecular features in all animals, but also some interesting convergent mechanisms. In this review, we will explore the current knowledge about the evolution of phagocytic and cytotoxic immune lineages against pathogens, in the clearance of damaged cells, for regeneration, for histocompatibility recognition, and in killing virally infected cells. To this end, we give different immune examples of multicellular organism models, ranging from the roots of bilateral organisms to chordate invertebrates, comparing to vertebrates' lineages. In this review, we compare cellular lineage homologies at the cellular and molecular levels. We aim to highlight and discuss the diverse function plasticity within the evolved immune effector cells, and even suggest the costs and benefits that it may imply for organisms with the meaning of greater defense against pathogens but less ability to regenerate damaged tissues and organs.


Assuntos
Linhagem da Célula , Doenças Transmissíveis/imunologia , Citotoxicidade Imunológica , Imunidade Celular , Imunidade Inata , Fagócitos/imunologia , Fagocitose , Animais , Bactérias/imunologia , Bactérias/patogenicidade , Doenças Transmissíveis/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Parasitos/imunologia , Parasitos/patogenicidade , Fagócitos/metabolismo , Transdução de Sinais , Vírus/imunologia , Vírus/patogenicidade
17.
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
18.
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
19.
J Adv Res ; 31: 61-74, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34194832

RESUMO

Background: Even though exosome-based therapy has been shown to be able to control the progression of different pathologies, the data revealed by pharmacokinetic studies warn of the low residence time of exogenous exosomes in circulation that can hinder the clinical translation of therapeutic exosomes. The macrophages related to the organs of the mononuclear phagocytic system are responsible primarily for the rapid clearance and retention of exosomes, which strongly limits the amount of exosomal particles available to reach the target tissue, accumulate in it and release with high efficiency its therapeutic cargo in acceptor target cells to exert the desired biological effect. Aim of review: Endowing exosomes with surface modifications to evade the immune system is a plausible strategy to contribute to the suppression of exosomal clearance and increase the efficiency of their targeted content delivery. Here, we summarize the current evidence about the mechanisms underlying the recognition and sequestration of therapeutic exosomes by phagocytic cells. Also, we propose different strategies to generate 'invisible' exosomes for the immune system, through the incorporation of different anti-phagocytic molecules on the exosomes' surface that allow increasing the circulating half-life of therapeutic exosomes with the purpose to increase their bioavailability to reach the target tissue, transfer their therapeutic molecular cargo and improve their efficacy profile. Key scientific concepts of review: Macrophage-mediated phagocytosis are the main responsible behind the short half-life in circulation of systemically injected exosomes, hindering their therapeutic effect. Exosomes 'Camouflage Cloak' strategy using antiphagocytic molecules can contribute to the inhibition of exosomal clearance, hence, increasing the on-target effect. Some candidate molecules that could exert an antiphagocytic role are CD47, CD24, CD44, CD31, ß2M, PD-L1, App1, and DHMEQ. Pre- and post-isolation methods for exosome engineering are compatible with the loading of therapeutic cargo and the expression of antiphagocytic surface molecules.


Assuntos
Mimetismo Biológico , Sistemas de Liberação de Medicamentos/métodos , Exossomos/metabolismo , Fagocitose , Antígeno B7-H1/metabolismo , Disponibilidade Biológica , Antígeno CD24/metabolismo , Antígeno CD47/metabolismo , Exossomos/imunologia , Humanos , Receptores de Hialuronatos/metabolismo , Sistema Imunitário , Macrófagos/imunologia , Macrófagos/metabolismo , Sistema Fagocitário Mononuclear/metabolismo , Fagócitos/imunologia , Fagócitos/metabolismo
20.
J Adv Res ; 31: 155-163, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34194839

RESUMO

Introduction: To enhance photothermal treatment (PTT) efficiency, a delivery method that uses cell vector for nanoparticles (NPs) delivery has drawn attention and studied widely in recent years. Objectives: In this study, we demonstrated the feasibility of M1 activated macrophage as a live vector for delivering NPs and investigated the effect of NPs loaded M1 stimulated by Lipopolysaccharide on PTT efficiency in vivo. Methods: M1 was used as a live vector for delivering NPs and further to investigate the effect of NPs loaded M1 on PTT efficiency. Non-activated macrophage (MФ) was stimulated by lipopolysaccharide (LPS) into M1 and assessed for tumor cell phagocytic capacity towards NPs. Results: We found M1 exhibited a 20-fold higher uptake capacity of NPs per cell volume and 2.9-fold more active infiltration into the tumor site, compared with non-activated macrophage MФ. We injected M1 cells peritumorally and observed that these cells penetrated into the tumor mass within 12 h. Then, we conducted PTT using irradiation of a near-infrared laser for 1 min at 1 W/cm2. As a result, we confirmed that using M1 as an active live vector led to a more rapid reduction in tumor size within 1 day indicating that the efficacy of PTT with NPs-loaded M1 is higher than that with NPs-loaded MФ. Conclusion: Our study demonstrated the potential role of M1 as a live vector for enhancing the feasibility of PTT in cancer treatment.


Assuntos
Ouro/farmacologia , Macrófagos/metabolismo , Nanopartículas/química , Neoplasias/terapia , Terapia Fototérmica/métodos , Animais , Linhagem Celular Tumoral , Ouro/química , Humanos , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fagócitos/metabolismo , Células RAW 264.7
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