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1.
Proc Natl Acad Sci U S A ; 120(15): e2220704120, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37014860

RESUMO

The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics.


Assuntos
Variações do Número de Cópias de DNA , Neoplasias , Feminino , Humanos , Metilação , 5-Metilcitosina , DNA/genética , Mutação , Neoplasias/genética , Metilação de DNA
2.
Cell ; 140(1): 148-60, 2010 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-20074523

RESUMO

Over 1 billion people are estimated to be overweight, placing them at risk for diabetes, cardiovascular disease, and cancer. We performed a systems-level genetic dissection of adiposity regulation using genome-wide RNAi screening in adult Drosophila. As a follow-up, the resulting approximately 500 candidate obesity genes were functionally classified using muscle-, oenocyte-, fat-body-, and neuronal-specific knockdown in vivo and revealed hedgehog signaling as the top-scoring fat-body-specific pathway. To extrapolate these findings into mammals, we generated fat-specific hedgehog-activation mutant mice. Intriguingly, these mice displayed near total loss of white, but not brown, fat compartments. Mechanistically, activation of hedgehog signaling irreversibly blocked differentiation of white adipocytes through direct, coordinate modulation of early adipogenic factors. These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals.


Assuntos
Proteínas de Drosophila/metabolismo , Proteínas Hedgehog/metabolismo , Obesidade/genética , Adipócitos Marrons/metabolismo , Adipócitos Brancos/metabolismo , Adipogenia , Animais , AMP Cíclico/metabolismo , Glucocorticoides/metabolismo , Humanos , Camundongos , Camundongos Knockout , Células Musculares/metabolismo , Proteínas Repressoras/genética
3.
Blood ; 119(17): 3879-89, 2012 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-22308290

RESUMO

Cytotoxic T lymphocytes kill target cells via the polarized secretion of cytotoxic granules at the immune synapse. The lytic granules are initially recruited around the polarized microtubule-organizing center. In a dynein-dependent transport process, the granules move along microtubules toward the microtubule-organizing center in the minus-end direction. Here, we found that a kinesin-1-dependent process is required for terminal transport and secretion of polarized lytic granule to the immune synapse. We show that synaptotagmin-like protein 3 (Slp3) is an effector of Rab27a in cytotoxic T lymphocytes and interacts with kinesin-1 through the tetratricopeptide repeat of the kinesin-1 light chain. Inhibition of the Rab27a/Slp3/kinesin-1 transport complex impairs lytic granule secretion. Our data provide further molecular insights into the key functional and regulatory mechanisms underlying the terminal transport of cytotoxic granules and the latter's secretion at the immune synapse.


Assuntos
Grânulos Citoplasmáticos/metabolismo , Cinesinas/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Sinapses/imunologia , Linfócitos T Citotóxicos/imunologia , Proteínas rab de Ligação ao GTP/metabolismo , Western Blotting , Células Cultivadas , Grânulos Citoplasmáticos/imunologia , Imunofluorescência , Humanos , Cinesinas/antagonistas & inibidores , Cinesinas/genética , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas do Tecido Nervoso , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas rab de Ligação ao GTP/genética , Proteínas rab27 de Ligação ao GTP
4.
Blood ; 119(15): 3458-68, 2012 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-22174160

RESUMO

The molecular mechanisms that underlie T-cell quiescence are poorly understood. In the present study, we report a primary immunodeficiency phenotype associated with MST1 deficiency and primarily characterized by a progressive loss of naive T cells. The in vivo consequences include recurrent bacterial and viral infections and autoimmune manifestations. MST1-deficient T cells poorly expressed the transcription factor FOXO1, the IL-7 receptor, and BCL2. Conversely, FAS expression and the FAS-mediating apoptotic pathway were up-regulated. These abnormalities suggest that increased cell death of naive and proliferating T cells is the main mechanism underlying this novel immunodeficiency. Our results characterize a new mechanism in primary T-cell immunodeficiencies and highlight a role of the MST1/FOXO1 pathway in controlling the death of human naive T cells.


Assuntos
Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Mutação , Proteínas Serina-Treonina Quinases/genética , Linfócitos T/fisiologia , Adolescente , Sobrevivência Celular/genética , Células Cultivadas , Criança , Pré-Escolar , Família , Feminino , Genes Recessivos/fisiologia , Humanos , Síndromes de Imunodeficiência/sangue , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Mutação/fisiologia , Linhagem , Linfócitos T/imunologia
5.
Immunol Rev ; 235(1): 10-23, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20536552

RESUMO

The granule-dependent cytotoxic activity of lymphocytes plays a critical role in the defense against virally infected cells and tumor cells. The importance of this cytotoxic pathway in immune regulation is evidenced by the severe and often fatal condition, known as hemophagocytic lymphohistiocytic syndrome (HLH) that occurs in mice and humans with genetically determined impaired lymphocyte cytotoxic function. HLH manifests as the occurrence of uncontrolled activation of T lymphocytes and macrophages infiltrating multiple organs. In this review, we focus on recent advances in the characterization of effectors regulating the release of cytotoxic granules, and on the role of this cytotoxic pathway in lymphocyte homeostasis and immune surveillance. Analysis of the mechanisms leading to the occurrence of hemophagocytic syndrome designates gamma-interferon as an attractive therapeutic target to downregulate uncontrolled macrophage activation, which sustains clinical and biological features of HLH.


Assuntos
Citotoxicidade Imunológica/genética , Células Matadoras Naturais/imunologia , Ativação Linfocitária/genética , Linfo-Histiocitose Hemofagocítica/genética , Linfócitos T Citotóxicos/imunologia , Animais , Modelos Animais de Doenças , Predisposição Genética para Doença , Humanos , Imunoterapia/métodos , Padrões de Herança , Interferon gama/imunologia , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Linfo-Histiocitose Hemofagocítica/terapia , Ativação de Macrófagos/genética , Camundongos , Linhagem , Fenótipo , Fatores de Risco , Vesículas Secretórias/imunologia
6.
Sci Transl Med ; 16(731): eadi3883, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38266106

RESUMO

We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the validation cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and eight common protein biomarkers detected 51% of the cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature-the global reduction of AluS subfamily elements in the circulating DNA of patients with solid cancer. We confirmed this reduction through the analysis of another independent dataset obtained with a different approach (whole-genome sequencing). The evaluation of Alu elements may therefore have the potential to enhance the performance of several methods designed for the earlier detection of cancer.


Assuntos
Neoplasias , Humanos , Reprodutibilidade dos Testes , Neoplasias/diagnóstico , Neoplasias/genética , Elementos Nucleotídeos Curtos e Dispersos , Aprendizado de Máquina , Aneuploidia
7.
Blood ; 118(6): 1570-8, 2011 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-21693760

RESUMO

Cytotoxic T lymphocytes (CTLs) kill target cells through the polarized release of lytic molecules from secretory lysosomes. Loss of munc13-4 function inhibits this process and causes familial hemophagocytic lymphohistiocytosis type 3 (FHL3). munc13-4 binds rab27a, but the necessity of the complex remains enigmatic, because studies in knockout models suggest separate functions. In the present study, we describe a noncanonical rab27a-binding motif in the N-terminus of munc13-4. Point mutants in this sequence have severely impaired rab27a binding, allowing dissection of rab27a requirements in munc13-4 function. The munc13-4-rab27a complex is not needed for secretory lysosome maturation, as shown by complementation in CTLs from FHL3 patients and in a mast cell line silenced for munc13-4. In contrast, fusion of secretory lysosomes with, and content release at the plasma membrane during degranulation, strictly required the munc13-4-rab27a complex. Total internal reflection fluorescence microscopy imaging revealed that the complex corrals motile secretory lysosomes beneath the plasma membrane during degranulation and controls their docking. The propensity to stall motility of secretory lysosomes is lost in cells expressing munc13-4 point mutants that do not bind rab27. In summary, these results uncovered a mechanism for tethering secretory lysosomes to the plasma membrane that is essential for degranulation in immune cells.


Assuntos
Lisossomos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação/genética , Células COS , Linhagem Celular Tumoral , Chlorocebus aethiops , Exocitose , Células HEK293 , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/metabolismo , Linfo-Histiocitose Hemofagocítica/patologia , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/genética , Microscopia Confocal , Microscopia de Fluorescência , Dados de Sequência Molecular , Complexos Multiproteicos/metabolismo , Mutação , Ligação Proteica , Homologia de Sequência de Aminoácidos , Linfócitos T Citotóxicos/metabolismo , Proteínas rab de Ligação ao GTP/genética , Proteínas rab27 de Ligação ao GTP
8.
Cell Rep Med ; 4(8): 101148, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37552989

RESUMO

It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.


Assuntos
Neoplasias do Sistema Nervoso Central , Humanos , Reação em Cadeia da Polimerase/métodos , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Técnicas de Amplificação de Ácido Nucleico , Elementos Nucleotídeos Curtos e Dispersos , Sistema Nervoso Central
9.
PLoS Pathog ; 3(11): e173, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18039029

RESUMO

Serratia marcescens is an entomopathogenic bacterium that opportunistically infects a wide range of hosts, including humans. In a model of septic injury, if directly introduced into the body cavity of Drosophila, this pathogen is insensitive to the host's systemic immune response and kills flies in a day. We find that S. marcescens resistance to the Drosophila immune deficiency (imd)-mediated humoral response requires the bacterial lipopolysaccharide O-antigen. If ingested by Drosophila, bacteria cross the gut and penetrate the body cavity. During this passage, the bacteria can be observed within the cells of the intestinal epithelium. In such an oral infection model, the flies succumb to infection only after 6 days. We demonstrate that two complementary host defense mechanisms act together against such food-borne infection: an antimicrobial response in the intestine that is regulated by the imd pathway and phagocytosis by hemocytes of bacteria that have escaped into the hemolymph. Interestingly, bacteria present in the hemolymph elicit a systemic immune response only when phagocytosis is blocked. Our observations support a model wherein peptidoglycan fragments released during bacterial growth activate the imd pathway and do not back a proposed role for phagocytosis in the immune activation of the fat body. Thanks to the genetic tools available in both host and pathogen, the molecular dissection of the interactions between S. marcescens and Drosophila will provide a useful paradigm for deciphering intestinal pathogenesis.


Assuntos
Modelos Animais de Doenças , Drosophila/microbiologia , Interações Hospedeiro-Patógeno/fisiologia , Intestinos/microbiologia , Infecções por Serratia/fisiopatologia , Serratia marcescens/patogenicidade , Animais , Drosophila/imunologia , Hemolinfa/microbiologia , Imuno-Histoquímica , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções por Serratia/imunologia , Serratia marcescens/imunologia
10.
Commun Integr Biol ; 5(1): 64-7, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22482013

RESUMO

Natural Killer (NK) cells and Cytotoxic T lymphocytes (CTL) are critical for the immune response against virus infections or transformed cells. They kill target cells via polarized exocytosis of lytic proteins from secretory lysosomes (SL). Rab27a and munc13-4 interact directly and are required for target cell killing. How they cooperate in the intricate degranulation process is not known. We identified critical residues in munc13-4 for rab27 interaction and tested binding mutants in several complementation assays. In a rat mast cell line we replaced endogenous munc13-4 with ectopically expressed munc13-4 constructs. Unlike wild type munc13-4, binding mutants fail to rescue ß-hexosaminidase secretion. In accord, expression of binding mutants in CTL of Familial Hemophagocytic Lymphohistiocytosis type 3 patients, does not rescue CD107 appearance on the plasma membrane. Total Internal Reflection Fluorescence (TIRF) imaging shows that munc13-4*rab27a restricts motility of SL in the subapical cytoplasm. We propose that rab27*munc13-4 tethers SL to the plasma membrane, a requirement for formation of a cognate SNARE complex for fusion.

11.
J Exp Med ; 209(13): 2323-30, 2012 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-23230001

RESUMO

DNA polymerase ε (Polε) is a large, four-subunit polymerase that is conserved throughout the eukaryotes. Its primary function is to synthesize DNA at the leading strand during replication. It is also involved in a wide variety of fundamental cellular processes, including cell cycle progression and DNA repair/recombination. Here, we report that a homozygous single base pair substitution in POLE1 (polymerase ε 1), encoding the catalytic subunit of Polε, caused facial dysmorphism, immunodeficiency, livedo, and short stature ("FILS syndrome") in a large, consanguineous family. The mutation resulted in alternative splicing in the conserved region of intron 34, which strongly decreased protein expression of Polε1 and also to a lesser extent the Polε2 subunit. We observed impairment in proliferation and G1- to S-phase progression in patients' T lymphocytes. Polε1 depletion also impaired G1- to S-phase progression in B lymphocytes, chondrocytes, and osteoblasts. Our results evidence the developmental impact of a Polε catalytic subunit deficiency in humans and its causal relationship with a newly recognized, inherited disorder.


Assuntos
DNA Polimerase II/genética , Ossos Faciais/anormalidades , Transtornos do Crescimento/enzimologia , Transtornos do Crescimento/genética , Síndromes de Imunodeficiência/enzimologia , Síndromes de Imunodeficiência/genética , Livedo Reticular/enzimologia , Livedo Reticular/genética , Adolescente , Adulto , Processamento Alternativo , Sequência de Bases , Estatura/genética , Proliferação de Células , Criança , Pré-Escolar , Cromossomos Humanos Par 12/genética , Consanguinidade , Análise Mutacional de DNA , DNA Polimerase II/deficiência , Feminino , França , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Expressão Gênica , Genes Recessivos , Humanos , Síndromes de Imunodeficiência/imunologia , Íntrons , Livedo Reticular/patologia , Masculino , Linhagem , Mutação Puntual , Proteínas de Ligação a Poli-ADP-Ribose , Síndrome , Adulto Jovem
12.
PLoS One ; 6(3): e14743, 2011 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-21390224

RESUMO

BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.


Assuntos
Drosophila melanogaster/imunologia , Drosophila melanogaster/microbiologia , Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Animais , Peptídeos Catiônicos Antimicrobianos/imunologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas de Transporte/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/imunologia , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/microbiologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Micrococcus luteus/efeitos dos fármacos , Micrococcus luteus/imunologia , Proteínas Opsonizantes/metabolismo , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Receptores de Superfície Celular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Solubilidade/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/imunologia
13.
Science ; 325(5938): 340-3, 2009 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-19520911

RESUMO

Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.


Assuntos
Drosophila melanogaster/genética , Drosophila melanogaster/microbiologia , Genoma de Inseto , Imunidade Inata/genética , Interferência de RNA , Infecções por Serratia/imunologia , Serratia marcescens/imunologia , Animais , Animais Geneticamente Modificados , Proliferação de Células , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/imunologia , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Hemócitos/imunologia , Hemócitos/metabolismo , Hemócitos/microbiologia , Homeostase , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Janus Quinases/genética , Janus Quinases/metabolismo , Modelos Animais , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Infecções por Serratia/genética , Infecções por Serratia/microbiologia , Serratia marcescens/fisiologia , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/fisiologia
14.
Cell ; 123(2): 335-46, 2005 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-16239149

RESUMO

Phagocytosis is a complex, evolutionarily conserved process that plays a central role in host defense against infection. We have identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila. Transcriptional silencing of the eater gene in a macrophage cell line led to a significant reduction in the binding and internalization of bacteria. Moreover, the N terminus of the Eater protein mediated direct microbial binding which could be inhibited with scavenger receptor ligands, acetylated, and oxidized low-density lipoprotein. In vivo, eater expression was restricted to blood cells. Flies lacking the eater gene displayed normal responses in NF-kappaB-like Toll and IMD signaling pathways but showed impaired phagocytosis and decreased survival after bacterial infection. Our results suggest that Eater is a major phagocytic receptor for a broad range of bacterial pathogens in Drosophila and provide a powerful model to address the role of phagocytosis in vivo.


Assuntos
Proteínas de Drosophila/fisiologia , Drosophila/microbiologia , Genes de Insetos , Proteínas de Insetos/fisiologia , Proteínas de Membrana/fisiologia , Fagocitose , Receptores de Superfície Celular/fisiologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Infecções Bacterianas/prevenção & controle , Drosophila/citologia , Drosophila/embriologia , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Embrião não Mamífero , Escherichia coli/patogenicidade , Citometria de Fluxo , Mutação da Fase de Leitura , Histidina/química , Hibridização In Situ , Proteínas de Insetos/química , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Macrófagos/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Dados de Sequência Molecular , Fases de Leitura Aberta , Interferência de RNA , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Homologia de Sequência de Aminoácidos , Serratia marcescens/patogenicidade
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