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1.
Life Sci ; 240: 117078, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759041

RESUMO

AIM: The cross regulation between neuroendocrine system, particularly Hypothalamus-Pituitary-Thyroid (HPT) axis and immune system during embryonic/early neonatal developmental stages shapes the functional attribute of immune response throughout the life. Thus, disruption of immune system was anticipated on exposure to thyroid disrupting pesticides (TDPs) mancozeb (MCZ) and fipronil (FPN) during critical windows of early postnatal days (PND) development. MAIN METHODS: Mice were exposed to MCZ and FPN as individual (0.5% LD 50 each) and as mixtures (0.25% and 0.5% LD 50 each) from PND 31 (initiation phase of immune response) till PND 60 (Maturation phase). Thyroxine (T4) supplementation was given from PND 51 to PND 60. Assessment was done at PND 61 as well as at PND 91 (adults). KEY FINDINGS: Plasma level of thyroid hormones (T3 and T4) was reduced but pituitary hormone (TSH) increased till adulthood on exposure to mixture pesticides but not on individual exposure. Mixture pesticides also increased body weight gain and reduced survival rate in adults. Exposure of individual pesticides exert immunotoxicity but more pronounced immune suppression was observed in mixture pesticides exposed group as reflected in reduced relative weight and cellularity in spleen and thymus, reduced in vitro mitogenic (Con A/LPS) response of splenocytes and thymocytes (reduced proliferative index and increased apoptotic/necrotic death). T4 supplementation ameliorated thyroid disruptive and immunotoxic effect of pesticides. SIGNIFICANCE: The additive/synergistic toxicity as well as hypothyroidism induced by mixture pesticides has produced pronounced immune suppression that reflected till adulthood. Supplementation of T4 prevented thyroid axis disruption mediated immunosuppression.


Assuntos
Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Sistema Imunitário/efeitos dos fármacos , Inseticidas/toxicidade , Maneb/toxicidade , Praguicidas/antagonistas & inibidores , Praguicidas/toxicidade , Pirazóis/toxicidade , Tiroxina/metabolismo , Tiroxina/uso terapêutico , Zineb/toxicidade , Animais , Peso Corporal , Feminino , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Análise de Sobrevida , Timo/citologia , Timo/efeitos dos fármacos , Timo/imunologia
2.
Immunology ; 159(1): 15-25, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31777069

RESUMO

The intricate host-microbial interaction and the overwhelming complexity of the mucosal immune system in the adult host raise the question of how this system is initially established. Here, we propose the implementation of the concept of the 'postnatal window of opportunity' into the model of a 'layered immunity' to explain how the newborn's mucosal immune system matures and how host-microbial immune homeostasis is established after birth. We outline the concept of a timed succession of non-redundant phases during postnatal immune development and discuss the possible influence of external factors and conditions.


Assuntos
Microbioma Gastrointestinal/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Sistema Imunitário/crescimento & desenvolvimento , Imunidade nas Mucosas , Mucosa Intestinal/microbiologia , Imunidade Adaptativa/imunologia , Animais , Homeostase/imunologia , Humanos , Imunidade Inata/imunologia , Recém-Nascido , Mucosa Intestinal/imunologia , Modelos Animais , Fatores de Tempo
3.
Adv Exp Med Biol ; 1185: 175-179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884608

RESUMO

We present evidence that protein citrullination, a proinflammatory and immune system-activating posttranslational modification (PTM) of arginine residues mediated by peptidyl arginine deiminases (PADs), is elevated in mouse models of retinal degenerations. Together with the fact that the animal models that we investigated (and their human counterparts) exhibit also anti-retinal autoantibodies, we propose that retinal citrullination is an immunogenic trigger that activates the immune system both locally and systemically, contributing to disease pathogenesis. Consistent with this possibility, we show that PAD compromise reduces the severity of Mertk-related retinal degeneration. Thus, PAD inhibition may be as a potential treatment strategy for retinal degenerations.


Assuntos
Autoimunidade , Citrulinação , Sistema Imunitário , Inflamação/patologia , Desiminases de Arginina em Proteínas/fisiologia , Degeneração Retiniana/patologia , Animais , Citrulina , Humanos , Camundongos
4.
Gan To Kagaku Ryoho ; 46(12): 1807-1813, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-31879393

RESUMO

Various microbes having been living in our intestine and forming the gut microbiome. When dysbiosis which is typically characterized by reduced microbial diversity occurs, many types of diseases are triggered in our bodies. Recently, relationship between gut microbiome and our immune function are discovered gradually. From this view point, the gut microbiome may have an influence on cancer medicine such as development, therapy(immune checkpoint blockade or chemotherapy), and therapeutic toxicity. In real clinical practice, this influence is reported in some cases such as colorectal cancer and other malignancies. In the near future, the approach from gut microbiome may be a clue to improve the existent cancer diagnosis and therapy. In addition, the modulation of gut microbiome in itself, for example fecal microbiota transplant(FMT), probiotics, and limited usage of antibiotics, is expected to be hints for cancer medicine, though this is not yet established and further studies are needed.


Assuntos
Microbioma Gastrointestinal , Disbiose , Transplante de Microbiota Fecal , Humanos , Sistema Imunitário
5.
Immunity ; 51(5): 794-811, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31747581

RESUMO

The consumption of Western-type calorically rich diets combined with chronic overnutrition and a sedentary lifestyle in Western societies evokes a state of chronic metabolic inflammation, termed metaflammation. Metaflammation contributes to the development of many prevalent non-communicable diseases (NCDs), and these lifestyle-associated pathologies represent a rising public health problem with global epidemic dimensions. A better understanding of how modern lifestyle and Western diet (WD) activate immune cells is essential for the development of efficient preventive and therapeutic strategies for common NCDs. Here, we review the current mechanistic understanding of how the Western lifestyle can induce metaflammation, and we discuss how this knowledge can be translated to protect the public from the health burden associated with their selected lifestyle.


Assuntos
Dieta Ocidental , Sistema Imunitário/fisiologia , Animais , Dieta , Suscetibilidade a Doenças , Retroalimentação Fisiológica , Microbioma Gastrointestinal , Homeostase , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Inflamação/etiologia , Inflamação/metabolismo , Especificidade de Órgãos
6.
Science ; 366(6465): 574-575, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672884
7.
Semin Oncol ; 46(4-5): 385-392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31739997

RESUMO

There is no doubt that immunotherapy lies in the spotlight of current cancer research and clinical trials. However, there are still limitations in the treatment response in certain types of tumors largely due to the presence of the complex network of immunomodulatory and immunosuppressive pathways. These limitations are not likely to be overcome by current immunotherapeutic options, which often target isolated steps in immune pathways preferentially involved in adaptive immunity. Recently, we have developed an innovative anti-cancer immunotherapeutic strategy that initially elicits a strong innate immune response with subsequent activation of adaptive immunity in mouse models. Robust primary innate immune response against tumor cells is induced by toll-like receptor ligands and anti-CD40 agonistic antibodies combined with the phagocytosis-stimulating ligand mannan, anchored to a tumor cell membrane by biocompatible anchor for membrane. This immunotherapeutic approach results in a dramatic therapeutic response in large established murine subcutaneous tumors including melanoma, sarcoma, pancreatic adenocarcinoma, and pheochromocytoma. Additionally, eradication of metastases and/or long-lasting resistance to subsequent re-challenge with tumor cells was also accomplished. Current and future advantages of this immunotherapeutic approach and its possible combinations with other available therapies are discussed in this review.


Assuntos
Imunoterapia , Neoplasias/terapia , Imunidade Adaptativa , Animais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Terapia Combinada , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunidade Inata , Imunomodulação , Imunoterapia/métodos , Ligantes , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Receptores Toll-Like/metabolismo , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
8.
Nat Rev Cancer ; 19(12): 667-685, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31645711

RESUMO

Resistance to cancer therapy remains a major challenge in clinical oncology. Although the initial treatment phase is often successful, eventual resistance, characterized by tumour relapse or spread, is discouraging. The majority of studies devoted to investigating the basis of resistance have focused on tumour-related changes that contribute to therapy resistance and tumour aggressiveness. However, over the last decade, the diverse roles of various host cells in promoting therapy resistance have become more appreciated. A growing body of evidence demonstrates that cancer therapy can induce host-mediated local and systemic responses, many of which shift the delicate balance within the tumour microenvironment, ultimately facilitating or supporting tumour progression. In this Review, recent advances in understanding how the host response to different cancer therapies may promote therapy resistance are discussed, with a focus on therapy-induced immunological, angiogenic and metastatic effects. Also summarized is the potential of evaluating the host response to cancer therapy in an era of precision medicine in oncology.


Assuntos
Carcinogênese , Resistencia a Medicamentos Antineoplásicos , Neoplasias/terapia , Animais , Antineoplásicos/farmacologia , Linhagem da Célula , Progressão da Doença , Intervalo Livre de Doença , Epigênese Genética , Humanos , Sistema Imunitário , Imunoterapia , Camundongos , Metástase Neoplásica , Recidiva Local de Neoplasia , Neovascularização Patológica , Medicina de Precisão , Microambiente Tumoral
9.
Sheng Li Xue Bao ; 71(5): 769-782, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646331

RESUMO

Autoimmune diseases are a kind of chronic diseases with unclear etiology, which has the characteristics of repetition and difficulty to cure completely. Aerobic exercise, as an effective intervention method for chronic diseases, has also received extensive attention in the field of the prevention and treatment of autoimmune diseases. In this paper, the effects of aerobic exercise on immune system and autoimmune diseases in recent years are reviewed, and the related mechanisms are discussed. It is pointed out that aerobic exercise can improve the homeostasis of immune environment by affecting the number and function of immune cells, inhibit the systemic inflammatory response of the body, and then delay the occurrence and development of autoimmune diseases.


Assuntos
Doenças Autoimunes/prevenção & controle , Exercício , Sistema Imunitário , Homeostase , Humanos
10.
Mol Biol (Mosk) ; 53(5): 815-829, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31661480

RESUMO

The modern era of research in immunology is characterized by an unprecedented level of detail about structural characteristics of the immune system and the regulation of activities of its numerous components, which function together as a whole distributed-parameter system. Mathematical modeling provides an analytical tool to describe, analyze, and predict the dynamics of immune responses by applying a reductionist approach. In modern systems immunology and mathematical immunology as a new interdisciplinary field, a great challenge is to formulate the mathematical models of the human immune system that reflect the level achieved in understanding its structure and describe the processes that sustain its function. To this end, a systematic development of multiscale mathematical models has to be advanced. An appropriate methodology should consider (1) the intracellular processes of immune cell fate regulation, (2) the population dynamics of immune cells in various organs, and (3) systemic immunophysiological processes in the whole host organism. Main studies aimed at modeling the intracellular regulatory networks are reviewed in the context of multiscale mathematical modelling. The processes considered determine the regulation of the immune cell fate, including activation, division, differentiation, apoptosis, and migration. Because of the complexity and high dimensionality of the regulatory networks, identifying the parsimonious descriptions of signaling pathways and regulatory loops is a pressing problem of modern mathematical immunology.


Assuntos
Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Modelos Imunológicos , Apoptose , Diferenciação Celular , Movimento Celular , Humanos , Transdução de Sinais
12.
Adv Exp Med Biol ; 1172: 207-226, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31628658

RESUMO

The NF-κB (Nuclear Factor kappa B) transcription factor plays crucial roles in the regulation of numerous biological processes including development of the immune system, inflammation, and innate and adaptive immune responses. Control over the immune cell functions of NF-κB results from signaling through one of two different routes: the canonical and noncanonical NF-κB signaling pathways. Present at the end of both pathways are the proteins NF-κB, IκB, and the IκB kinase (IKK). These proteins work together to deliver the myriad outcomes that influence context-dependent transcriptional control in immune cells. In the present chapter, we review the structural information available on NF-κB, IκB, and IKK, the critical terminal components of the NF-κB signaling, in relation to their physiological function.


Assuntos
Quinase I-kappa B , Proteínas I-kappa B , Sistema Imunitário , NF-kappa B , Transdução de Sinais , Animais , Humanos , Quinase I-kappa B/imunologia , Proteínas I-kappa B/imunologia , Sistema Imunitário/enzimologia , NF-kappa B/imunologia , Fosforilação , Transdução de Sinais/imunologia
13.
Cytogenet Genome Res ; 159(2): 55-65, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31630146

RESUMO

Klinefelter syndrome (KS) is one of the most common congenital disorders of male infertility. Given its high heterogeneity in clinical and genetic presentation, the relationship between transcriptome, clinical phenotype, and associated co-morbidities seen in KS has not been fully clarified. Here, we report a 47,XXY Chinese male with infertility and analyzed the differences in gene expression patterns of peripheral blood mononuclear cells (PBMCs) with regard to a Chinese male and a female control with normal karyotype by single-cell sequencing. A total of 24,439 cells were analyzed and divided into 5 immune cell types (including B cells, T cells, macrophage cells, dendritic cells, and natural killer cells) according to marker genes. Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells between the KS patient and both controls. Gene ontology enrichment analyses yielded terms associated with well-known comorbidities seen in KS as well as an affected immune system and type I diabetes mellitus. Based on our data, we identified several candidate genes which may be implicated in regulating the phenotype of KS. Overall, this analysis provides a comprehensive map of the cell types of PBMCs in a KS patient at the single-cell level, which will contribute to the prevention of comorbidity and improvement of the life quality of KS patients.


Assuntos
Síndrome de Klinefelter/genética , Feminino , Expressão Gênica/genética , Expressão Gênica/imunologia , Genótipo , Humanos , Sistema Imunitário/imunologia , Infertilidade Masculina/genética , Infertilidade Masculina/imunologia , Síndrome de Klinefelter/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/fisiologia , Masculino , Fenótipo , Análise de Célula Única/métodos , Transcriptoma/genética , Transcriptoma/imunologia
14.
Rev Cardiovasc Med ; 20(3): 153-160, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601089

RESUMO

Exosomes, nanosized lipid bilayer membranous vesicles, are secreted by a variety of cells and contain protein, lipids, mRNA, miRNA, and signaling molecules that participate in intercellular material transfer and information exchange through binding, fusion or endocytosis. Exosomes mediate the gene expression of target cells and regulate pathological and physiological processes, thereby playing a key role in the occurrence and development of various diseases. Accumulated studies has shown that exosomes hold therapeutic potential though their anti-apoptotic and anti-fibrotic roles. They also have been shown to promote angiogenesis, inhibit ventricular remodeling and improve cardiac function, as well as inhibiting local inflammation and regulating the immune response. As such, exosomes represent a new target for the treatment of cardiovascular diseases. This review summarizes the literature in this field to date, including the basic biological characteristics of exosomes, and new progress in the understanding of the mechanisms of their involvement in immune regulation in cardiovascular diseases. In this way, it servrs as a basis for future research and the development of therapeutic exosomes.


Assuntos
Doenças Cardiovasculares/imunologia , Sistema Cardiovascular/imunologia , Exossomos/imunologia , Sistema Imunitário/imunologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Exossomos/metabolismo , Exossomos/transplante , Humanos , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Prognóstico , Transdução de Sinais
15.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3374-3383, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602898

RESUMO

Traditional Chinese medicine Tripterygium wilfordii Hook.f( TWHF) is a natural botanical drug in China. It has complex chemical compositions and has been used for a long history. TWHF was used as an insecticide to protect crops at early stage,and it was later found to have significant effects in the treatment of rheumatoid arthritis,attaining great concerns. With further researches,it was found that TWHF can treat various diseases in the medical field due to a variety of pharmacological activities such as anti-cancer,neuroprotection,anti-inflammatory and immune-suppressing,particularly. Multiple extracts of TWHF have unique immunosuppressive function,playing an immune role through multi-target and multi-channel,with significant effect in the treatment of autoimmune diseases. As an immune-suppressing drug,TWHF is worthy of in-depth research due to its broad application prospects. While achieving good clinical efficacy,reports about its toxic effects to multiple systems of the body are also increasing,greatly hindering its clinical application. In order to fully understand the immune-suppressing function of TWHF and reduce or avoid the occurrence of toxic and side effects,we summarized recent progress of TWHF on the immune organs,cells and factors in recent years,as well as the pharmacology and toxic effects,hoping to provide a scientific and reasonable reference for its wider use in clinical treatment.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Sistema Imunitário/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tripterygium/química , Artrite Reumatoide/tratamento farmacológico , Humanos
16.
Life Sci ; 238: 116923, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610191

RESUMO

Idiopathic membranous nephropathy (IMN) has recently attracted much attention due to the development of auto antibodies, anti-phospholipase A2 receptor and anti-thrombospondin type I domain-containing 7A on podocytes, the establishment of immune networks complexes in circulation as well as the development of autoreactive immune cells against kidney, in both innate and adaptive participants. The auto inflammatory responses in IMN leads to the dysfunction of glomerular cells to represent pathological status. T cells, as a crucial factor in the immune network, support B cell-related responses and develop inflammation and cytotoxicity. They have the most determining roles in the autoimmune diseases. Activation of T cells occurs just before their infiltration in kidney. This process is definitely accompanied by costimulatory factors and cytokines, in order to develop and increase the number of these cells. In addition, altered B cell signaling network by the B cell receptor and co receptors such as B cell-activating factor receptor (BAFFR) stimulates the autoimmune-related pathogenesis. Autoantigens exposure and kidney infiltration of naive T cells lead to their local development. Furthermore, losing peripheral immune tolerance towards kidney antigens, will result in IMN. The growing findings about different immune system factors, cells and molecular mechanism have also revealed new pathways of pathogenesis and diagnosis approaches, such as personalized medicine in MN patients. This review aims to discuss the recent findings in adaptive immune cells, and distinguishes between intact and undone researches about pathogenesis and molecular signaling pathways of immune system in MN disease.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/patologia , Sistema Imunitário/imunologia , Animais , Humanos
17.
Vet Clin North Am Food Anim Pract ; 35(3): 485-505, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590899

RESUMO

New insights into the host-microbiota relationship have recently emerged with the advancement of molecular technologies such as next-generation sequencing. This article presents the current knowledge regarding the interaction between bacteria and the immune system of the gut, the uterus, and the mammary gland of cattle.


Assuntos
Bovinos/imunologia , Bovinos/microbiologia , Sistema Imunitário/microbiologia , Microbiota/imunologia , Animais , Feminino , Imunidade nas Mucosas/imunologia
18.
Vet Clin North Am Food Anim Pract ; 35(3): 507-534, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590900

RESUMO

Livestock industries strive to improve the health of their animals and, in the future, they are going to be required to do this with a continued reduction in antimicrobial use. Nutraceuticals represent a group of compounds that may help fill that void because they exert some health benefits when supplemented to livestock. This review is focused on the mechanisms of action, specifically related to the immune responses and health of ruminants. The nutraceutical classes discussed include probiotics, prebiotics, phytonutrients (essential oils and spices), and polyunsaturated fatty acids.


Assuntos
Ração Animal , Bovinos/fisiologia , Suplementos Nutricionais , Animais , Anti-Infecciosos/administração & dosagem , Bovinos/imunologia , Bovinos/microbiologia , Sistema Imunitário/efeitos dos fármacos , Prebióticos/administração & dosagem , Probióticos/administração & dosagem
19.
Nat Commun ; 10(1): 4298, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541102

RESUMO

Insecticidal fungi represent a promising alternative to chemical pesticides for disease vector control. Here, we show that the pathogenic fungus Beauveria bassiana exports a microRNA-like RNA (bba-milR1) that hijacks the host RNA-interference machinery in mosquito cells by binding to Argonaute 1 (AGO1). bba-milR1 is highly expressed during fungal penetration of the mosquito integument, and suppresses host immunity by silencing expression of the mosquito Toll receptor ligand Spätzle 4 (Spz4). Later, upon entering the hemocoel, bba-milR1 expression is decreased, which avoids induction of the host proteinase CLIPB9 that activates the melanization response. Thus, our results indicate that the pathogen deploys a cross-kingdom small-RNA effector that attenuates host immunity and facilitates infection.


Assuntos
Beauveria/imunologia , Interações Hospedeiro-Patógeno/imunologia , MicroRNAs/metabolismo , Mosquitos Vetores/imunologia , Mosquitos Vetores/microbiologia , Animais , Anopheles/imunologia , Anopheles/microbiologia , Beauveria/patogenicidade , Feminino , Perfilação da Expressão Gênica , Sistema Imunitário/imunologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Malária/imunologia , Controle Biológico de Vetores , Interferência de RNA , RNA de Cadeia Dupla
20.
Nat Commun ; 10(1): 4295, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541153

RESUMO

Sexual dimorphism in the mammalian immune system is manifested as more frequent and severe infectious diseases in males and, on the other hand, higher rates of autoimmune disease in females, yet insights underlying those differences are still lacking. Here we characterize sex differences in the immune system by RNA and ATAC sequence profiling of untreated and interferon-induced immune cell types in male and female mice. We detect very few differentially expressed genes between male and female immune cells except in macrophages from three different tissues. Accordingly, very few genomic regions display differences in accessibility between sexes. Transcriptional sexual dimorphism in macrophages is mediated by genes of innate immune pathways, and increases after interferon stimulation. Thus, the stronger immune response of females may be due to more activated innate immune pathways prior to pathogen invasion.


Assuntos
Sistema Imunitário , Caracteres Sexuais , Transcriptoma , Animais , Biologia Computacional , Epigenômica , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genômica , Humanos , Imunidade Inata/genética , Interferons/metabolismo , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos , RNA , Fatores Sexuais
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