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1.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1104-1113, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856424

RESUMO

Here, we present a technique that predicts the radiation's distribution in any optical system. It is based on decomposing the emitting source power by assigning a fraction of the total power to each emitted ray. All kinds of power losses in the rays' optical paths are considered. Fractioned radiation patterns are created in the last optical system surface, each associated with a single ray. We refer to fractioned patterns as those that conform to a whole radiating pattern. Thus, the irradiance of the completely illuminated surface is calculated by adding the optical system's fractioned radiation maps. This method is non-zero étendue. The result presented here allows for predicting the radiation patterns accurately with a handful of equations and can help design any image and non-image-forming optical systems.

2.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1114-1121, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856425

RESUMO

In Part I, the authors proposed a theoretical background for predicting the radiation distribution in any optical system based on decomposing the emitting source power. Here, we describe the validity of this decomposition through a practical example that uses a radiating source and a single surface optical system. This source is calibrated in a metrology testbed that guarantees its traceability to the candela (cd), the International System (SI) base unit for luminous intensity I v. A second example, this time numerical, shows the method's performance in a multisurface optical system.

3.
J Cell Biochem ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38924562

RESUMO

Prostaglandin F2 receptor negative regulator (PTGFRN) is a transmembrane protein associated with metastatic characteristics of certain cancer types. However, it remains poorly characterized and its direct function in cancer remains unclear. The study presented here aims to further examine whether PTGFRN expression affects a cancer cell's phenotype, as well as metastatic-like characteristics. We used stable shRNA and cDNA transfections to respectively knockdown and overexpress PTGFRN in three different cancer cell lines, two of which are representative of rare and aggressive cancers (Mesothelioma and Pediatric Medulloblastoma). We then examined the characteristics of the resulting clones and showed a decrease in proliferation, migration, colony formation, and spheroid growth capabilities in cells where PTGFRN expression had been inhibited, while cells overexpressing PTGFRN showed the opposite. In addition, we showed that PTGFRN displayed direct binding to two protein partners, Integrin ß1 and E. Cadherin, the latter of which is a novel direct binding partner to PTGFRN. Furthermore, silencing PTGFRN expression impacted the cellular process of autophagy, thereby providing another avenue by which PTGFRN potentially contributes to a cancer cell phenotype. Our findings demonstrate the potential role of PTGFRN in cancer metastasis and suggest PTGFRN as a future target for drug development in the treatment of metastatic cancers.

4.
SAGE Open Med Case Rep ; 12: 2050313X241245281, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595944

RESUMO

Reversed flow in the basilar artery can be acquired or congenital. Acquired reversed flow in the basilar artery can result from acute thrombosis of the basilar artery or retrograde vertebral artery flow. Congenital continuous retrograde basilar artery flow has not been described. We report a 2-day-old male presenting with hypocalcemic seizures which led us to obtain a Duplex echoencephalogram. An echocardiogram was subsequently ordered. In the coronal plane through the anterior fontanelle, retrograde flow was seen in the basilar artery and the right vertebral artery. In the axial plane through the temporal window, the flow was anteroposterior in both posterior communicating arteries. In the posterior cerebral arteries, the flow was retrograde in the P1 segment and anterograde in the P2 and P3 segments. An interrupted aortic arch was suspected. The echocardiogram showed a large perimembranous ventricular septal defect with bidirectional shunting, a hypoplastic and bicuspid aortic valve, an aortic arch interrupted between the left common carotid artery and the left subclavian artery (type B interrupted aortic arch), and a 5 mm patent ductus arteriosus with predominant right to left flow. Because of the patency of the large patent ductus arteriosus, our patient showed no sign of posterior circulation insufficiency. Prostaglandin E1 therapy was initiated immediately. Diagnosis of DiGeorge syndrome was proven. The infant underwent interrupted aortic arch repair and anterograde flow was established in the basilar artery. We conclude that congenital asymptomatic continuous retrograde flow in the basilar artery and left vertebral artery is a medical emergency as it implies the presence of type B interrupted aortic arch with large patent ductus arteriosus in a neonate.

5.
ACS Omega ; 9(12): 14381-14387, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38559916

RESUMO

Prostaglandin F2 receptor negative regulator (PTGFRN) is a transmembrane protein whose expression has been previously implicated in cancer metastasis. However, the exact molecular mechanisms by which PTGFRN influences cancer progression are still unknown. As such, our laboratory set out to investigate how PTGFRN knockdown affected the expression of other proteins. We also carried out coimmunoprecipitation experiments using a monoclonal anti-PTGFRN antibody. We employed mass spectrometry-based proteomics for both experiments to identify proteins that were associated with PTGFRN. Our data show that PTGFRN knockdown increased pathways related to innate immune responses and decreased pathways associated with the synthesis of metabolic precursors and protein processing, among others. Additionally, the coimmunoprecipitation experiments indicated that PTGFRN is associated with proteins involved in processing and metabolism, as well as VEGF signaling molecules. These results highlight the role of PTGFRN as a protein processing regulator, which may be influencing cancer progression.

6.
Mar Biotechnol (NY) ; 26(1): 1-18, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38153608

RESUMO

The increased knowledge of functional foods has led to the development of a new generation of health products, including those containing probiotics and products derived from them. Shewanella putrefaciens Pdp11 (SpPdp11) is a strain described as a probiotic that exerts important beneficial effects on several farmed fish. However, the use of live probiotic cells in aquaculture has limitations such as uncertain survival and shelf life, which can limit their efficacy. In addition, its efficacy can vary across species and hosts. When probiotics are administered orally, their activity can be affected by the environment present in the host and by interactions with the intestinal microbiota. Furthermore, live cells can also produce undesired substances that may negatively impact the host as well as the risk of potential virulence reversion acquired such as antibiotic resistance. Therefore, new alternatives emerged such as postbiotics. Currently, there is no knowledge about the postbiotic potential of SpPdp11 in the aquaculture industry. Postbiotic refers to the use of bacterial metabolites, including extracellular products (ECPs), to improve host physiology. However, the production of postbiotic metabolites can be affected by various factors such as cultivation conditions, which can affect bacterial metabolism. Thus, the objective of this study was to evaluate the postbiotic potential of ECPs from SpPdp11 under different cultivation conditions, including culture media, temperature, growth phase, and salinity. We analyzed their hydrolytic, antibacterial, antiviral, and cytotoxic capacity on several fish cell lines. The results obtained have demonstrated how each ECP condition can exert a different hydrolytic profile, reduce the biofilm formation by bacterial pathogens relevant to fish, lower the titer of nervous necrosis virus (NNV), and exert a cytotoxic effect on different fish cell lines. In conclusion, the ECPs obtained from SpPdp11 have different capacities depending on the cultivation conditions used. These conditions must be considered in order to recover the maximum number of beneficial capacities or to choose the appropriate conditions for specific activities.


Assuntos
Microbioma Gastrointestinal , Probióticos , Shewanella putrefaciens , Animais , Shewanella putrefaciens/fisiologia , Probióticos/farmacologia , Antibacterianos
7.
Animals (Basel) ; 13(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37958080

RESUMO

The use of functional feeds in aquaculture is currently increasing. This study aimed to assess the combined impact of dietary green microalgae Chlorella fusca and ethanol-inactivated Vibrio proteolyticus DCF12.2 (CVP diet) on thick-lipped grey mullet (Chelon labrosus) juvenile fish. The effects on intestinal microbiota and the transcription of genes related to metabolism, stress, and the immune system were investigated after 90 days of feeding. Additionally, the fish were challenged with Aeromonas hydrophila and polyinosinic-polycytidylic acid (poly I:C) to evaluate the immune response. Microbiota analysis revealed no significant differences in alpha and beta diversity between the anterior and posterior intestinal sections of fish fed the control (CT) and CVP diets. The dominant genera varied between the groups; Pseudomonas and Brevinema were most abundant in the CVP group, whereas Brevinema, Cetobacterium, and Pseudomonas were predominant in the CT group. However, microbial functionality remained unaltered. Gene expression analysis indicated notable changes in hif3α, mhcII, abcb1, mx, and tnfα genes in different fish organs on the CVP diet. In the head kidney, gene expression variations were observed following challenges with A. hydrophila or poly I:C, with higher peak values seen in fish injected with poly I:C. Moreover, c3 mRNA levels were significantly up-regulated in the CVP group 72 h post-A. hydrophila challenge. To conclude, incorporating C. fusca with V. proteolyticus in C. labrosus diet affected the microbial species composition in the intestine while preserving its functionality. In terms of gene expression, the combined diet effectively regulated the transcription of stress and immune-related genes, suggesting potential enhancement of fish resistance against stress and infections.

8.
Nat Commun ; 14(1): 5671, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704658

RESUMO

The primary cilium is a signaling organelle with a unique membrane composition maintained by a diffusional barrier residing at the transition zone. Many transition zone proteins, such as the tectonic complex, are linked to preserving ciliary composition but the mechanism remains unknown. To understand tectonic's role, we generate a photoreceptor-specific Tctn1 knockout mouse. Loss of Tctn1 results in the absence of the entire tectonic complex and associated MKS proteins yet has minimal effects on the transition zone structure of rod photoreceptors. We find that the protein composition of the photoreceptor cilium is disrupted as non-resident membrane proteins accumulate in the cilium over time, ultimately resulting in photoreceptor degeneration. We further show that fluorescent rhodopsin moves faster through the transition zone in photoreceptors lacking tectonic, which suggests that the tectonic complex acts as a physical barrier to slow down membrane protein diffusion in the photoreceptor transition zone to ensure proper removal of non-resident membrane proteins.


Assuntos
Cílios , Proteínas de Membrana , Animais , Camundongos , Proteínas de Membrana/genética , Rodopsina/genética , Neuritos , Corantes , Camundongos Knockout
10.
Pharmaceuticals (Basel) ; 16(5)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37242444

RESUMO

One of the main bioactive compounds of interest from the Ulva species is the sulfated polysaccharide ulvan, which has recently attracted attention for its anticancer properties. This study investigated the cytotoxic activity of ulvan polysaccharides obtained from Ulva rigida in the following scenarios: (i) in vitro against healthy and carcinogenic cell lines (1064sk (human fibroblasts), HACAT (immortalized human keratinocytes), U-937 (a human leukemia cell line), G-361 (a human malignant melanoma), and HCT-116 (a colon cancer cell line)) and (ii) in vivo against zebrafish embryos. Ulvan exhibited cytotoxic effects on the three human cancer cell lines tested. However, only HCT-116 demonstrated sufficient sensitivity to this ulvan to make it relevant as a potential anticancer treatment, presenting an LC50 of 0.1 mg mL-1. The in vivo assay on the zebrafish embryos showed a linear relationship between the polysaccharide concentration and growth retardation at 7.8 hpf mL mg-1, with an LC50 of about 5.2 mg mL-1 at 48 hpf. At concentrations near the LC50, toxic effects, such as pericardial edema or chorion lysis, could be found in the experimental larvae. Our in vitro study supports the potential use of polysaccharides extracted from U. rigida as candidates for treating human colon cancer. However, the in vivo assay on zebrafish indicated that the potential use of ulvan as a promising, safe compound should be limited to specific concentrations below 0.001 mg mL-1 since it revealed side effects on the embryonic growth rate and osmolar balance.

11.
Animals (Basel) ; 13(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36830376

RESUMO

This study aimed to evaluate the combined effect of dietary Chlorella fusca and ethanol-inactivated Vibrio proteolyticus DCF12.2 (C + V diet) in Chelon labrosus juveniles, highlighting their nutritional, physiological, and morphological effects. The results showed that the combined dietary inclusion of C. fusca and V. proteolyticus significantly enhanced growth performance and feed utilization compared to the control group. The C + V diet increased the fish lipid quality index (FLQ), n-3 polyunsaturated fatty acids, and n-3/n-6 ratio, which might be beneficial in terms of human nutrition. The C + V diet considerably increased carbohydrate metabolic activity by statistically boosting plasma glucose. The dietary inclusion of C. fusca in conjunction with V. proteolyticus increased metabolic enzyme activity as well as intestinal absorption capacity compared to that found in the control group. In conclusion, the experimental diet was suitable for feeding C. labrosus, increasing their growth and the nutritional characteristics of the muscle and intestine, without causing tissue damage.

12.
Microorganisms ; 11(2)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36838428

RESUMO

Given the potential of microalgae as new aquafeed ingredients, this study focuses on using a blend of microalgae, Tisochrysis lutea, Nannochloropsis gaditana, and Scenedesmus almeriensis, as a dietary ingredient for feeding Sparus aurata juveniles. The growth performance, carcass composition, tissue fatty acid profile, and intestinal microbiota were evaluated after a 30 day-feeding period. A microalgae-free diet was used as control, and three experimental diets were formulated containing 5%, 15%, and 25% of the microalgae blend (MB-5%, MB-15%, and MB-25%, respectively). After 7, 15, and 30 days of feeding experimental diets, biological samples were taken. Growth performance and nutrient utilization were not significantly modified at the end of the experiment. Microalgae inclusion tended to decrease body lipids and affected the fatty acid profile, especially MB-25 diet increased DHA levels. Diet MB-25 promoted appropriate microbial diversity, favoring the presence of probiotic bacteria, such as Lactobacillus, and significantly influencing the fatty acid composition and lipid metabolism in fish. In conclusion, using a short pulse of dietary administration of 25% microalgal blend in S. aurata modulates the intestinal microbiota and lipid composition while maintaining growth performance.

13.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1537058

RESUMO

La producción ovina en los últimos años en Colombia, se considera como una actividad con miras a exportación de carne, por lo cual, es necesario conocer el desempeño productivo de las diferentes razas dedicadas a este propósito en las regiones, con un número considerable de animales respecto al inventario nacional; por lo tanto, el objetivo de esta investigación fue describir el crecimiento en ovinos de pelo colombiano en los departamentos de Córdoba y Cesar, Colombia. Se utilizaron 99 animales de los biotipos Sudán y Etíope. Fueron evaluados los modelos Gompertz, Von Bertalanffy, Brody y Logístico. Los parámetros para obtener las curvas de crecimiento fueron estimados por medio del procedimiento NLIN de SAS. Utilizando el modelo de mejor ajuste, se determinó el porcentaje y la edad de madurez. El modelo Brody fue el que mejor ajustó los datos. El sexo no tuvo efecto significativo sobre los parámetros estimados, mientras que el biotipo racial fue significativo para todos los parámetros estimados, con la excepción de ß 1 ; la zona presentó efecto significativo sobre ß 0 y ß 2 y la época solo para ß 1. De acuerdo con los parámetros de la curva Brody estimados y a los porcentajes y edades a la madurez, en las poblaciones en estudio, se debe mejorar la alimentación de los animales e implementar un programa de selección, con el fin de mejorar los pesos de los animales, al llegar a la edad adulta.


Sheep production in recent years in Colombia is considered as an activity for the exportation of meat, therefore, it is necessary to know the productive performance of the different breeds dedicated to this purpose in the regions with a considerable number of animals with respect to national inventory. Therefore, the purpose of this research was to describe the growth in Colombian hair sheep in the departments of Cordoba and Cesar, Colombia. 99 animals of the Sudan and Ethiopian biotypes were used. The Gompertz, Von Bertalanffy, Brody and Logistic models were evaluated. The parameters of the growth curves were estimated by the procedure NLIN of SAS. Using the best fit model, the percentage and age of maturity were determined. The Brody model was the one that best fit the data. Sex had no significant effect on the estimated parameters, while racial biotype was significant for all estimated parameters, with the exception of ß 1; the zone presented a significant effect on ß 0 and ß 2; and the season only for ß 1. According to the estimated parameters of the Brody curve and the percentages and ages at maturity, in the populations under study, the feeding of the animals should be improved and a conduct a selection program, in order to improve the weights of the animals at reach adulthood.

14.
Blood ; 139(19): 2855-2870, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35357446

RESUMO

The leukocyte NADPH oxidase 2 (NOX2) plays a key role in pathogen killing and immunoregulation. Genetic defects in NOX2 result in chronic granulomatous disease (CGD), associated with microbial infections and inflammatory disorders, often involving the lung. Alveolar macrophages (AMs) are the predominant immune cell in the airways at steady state, and limiting their activation is important, given the constant exposure to inhaled materials, yet the importance of NOX2 in this process is not well understood. In this study, we showed a previously undescribed role for NOX2 in maintaining lung homeostasis by suppressing AM activation, in CGD mice or mice with selective loss of NOX2 preferentially in macrophages. AMs lacking NOX2 had increased cytokine responses to Toll-like receptor-2 (TLR2) and TLR4 stimulation ex vivo. Moreover, between 4 and 12 week of age, mice with global NOX2 deletion developed an activated CD11bhigh subset of AMs with epigenetic and transcriptional profiles reflecting immune activation compared with WT AMs. The presence of CD11bhigh AMs in CGD mice correlated with an increased number of alveolar neutrophils and proinflammatory cytokines at steady state and increased lung inflammation after insults. Moreover, deletion of NOX2 preferentially in macrophages was sufficient for mice to develop an activated CD11bhigh AM subset and accompanying proinflammatory sequelae. In addition, we showed that the altered resident macrophage transcriptional profile in the absence of NOX2 is tissue specific, as those changes were not seen in resident peritoneal macrophages. Thus, these data demonstrate that the absence of NOX2 in alveolar macrophages leads to their proinflammatory remodeling and dysregulates alveolar homeostasis.


Assuntos
Doença Granulomatosa Crônica , Pulmão , Macrófagos Alveolares , NADPH Oxidase 2 , Animais , Citocinas , Doença Granulomatosa Crônica/genética , Homeostase , Pulmão/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidase 2/genética
15.
J Opt Soc Am A Opt Image Sci Vis ; 39(1): 107-114, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35200980

RESUMO

A diffraction-limited lens having both surfaces conic is shown. The analytical and numerical calculation for all possible solutions of the conical front and back surfaces is presented. Object and image distances, lens thickness, and refractive index are prescribed. The process to obtain on-axis diffraction-limited images with bi-conic lenses and the proof of the method, corroborated through an example in Oslo, are described here.

16.
Alerta (San Salvador) ; 5(1): 6-11, ene. 28, 2022. ilus
Artigo em Espanhol | BISSAL, LILACS | ID: biblio-1354292

RESUMO

El quiste paraovárico se desarrolla en el ligamento ancho, entre la trompa de Falopio y el ovario. Son estructuras redondeadas de pared lisa, llenas de líquido seroso, que se ubican en el mesosálpinx, el ligamento ancho o sobre la propia trompa uterina. Tienen una incidencia aproximada de 1 en 1 500 0002 son frecuentes en la tercera y cuarta década de la vida; raramente se presentan en la edad pediátrica. Generalmente, son benignos y tiene un crecimiento lento y progresivo, suelen ser asintomáticos por lo que el diagnóstico suele ser incidental. En casos de quistes de gran volumen, los síntomas son dolor pélvico o la tumoración ab-dominal. Usualmente son diagnosticados clínicamente y se confirman por imágenes ultrasonográficas. La importancia de este caso es la poca frecuencia de estos tumores en la edad pediátrica y su identificación oportuna por parte de los profesionales de la salud


The paraovarian cyst develops in the broad ligament, between the fallopian tube and the ovary. They are rounded structures with a smooth wall, filled with serous fluid, which are located in the mesosalpinx, the broad ligament or on the uterine tube itself. They have an approximate incidence of 1 in 1,500,0002 and are common in the third and fourth decades of life; they rarely occur in childhood. Generally, they are benign and have a slow and progressive growth, they are usually asymptomatic, so the diagnosis is usually incidental. In cases of large volume cysts, the symptoms are pelvic pain or abdominal mass. They are usually diagnosed clinically and confirmed by ultrasonographic images. The importance of this case is the infrequency of these tumors in the pediatric age and their timely identification by health professionals


Assuntos
Cisto Parovariano , Pediatria , Diagnóstico , Ovário , Ligamento Largo , Dor Pélvica
17.
Mar Drugs ; 21(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36662178

RESUMO

The biochemical composition, molecular diversity, and two different bioactivities of Asparagopsis armata and Rugulopteryx okamurae (two alien species with different invasive patterns in the southern Iberian Peninsula) were analyzed through spectrophotometric methods and Fourier transform ion cyclotron mass spectroscopy (FT-ICR-MS). A total of 3042 molecular formulas were identified from the different extracts. The dH2O extracts were the most molecularly different. A. armata presented the highest content of nitrogenous compounds (proteins, CHON) and sulphur content, whereas R. okamurae was rich in carbonated compounds (total carbon, lipids, CHO, and CHOP). Antioxidant capacity and phenolic content were higher in R. okamurae than in A. armata. Antimicrobial activity was detected from both species. A. armata showed capacity to inhibit human and fish pathogens (e.g., Staphylococcus aureus or Vibrio anguillarum), whereas R. okamurae only showed inhibition against human bacteria (Staphylococcus aureus and Cutibacterium acnes). In R. okamurae, molecules with a great number of pharmaceutical activities (e.g., anti-inflammatory or antitumoral), antibacterial, biomaterial, and other utilities were found. The main molecules of A. armata had also pharmaceutical applications (e.g., antimalarian, antithrombotic, anti-inflammatory, or antiarthritis). The valorization of these species can help to counteract the environmental effects of the bioinvasions.


Assuntos
Phaeophyceae , Rodófitas , Animais , Humanos , Espécies Introduzidas , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Preparações Farmacêuticas , Extratos Vegetais/farmacologia , Extratos Vegetais/química
18.
Animals (Basel) ; 11(7)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34359240

RESUMO

The thick-lipped grey mullet (Chelon labrosus) is a nominee fish species for aquaculture diversification in Spain because it is an omnivore and euryhaline species, but limited knowledge about the nutritional attributes of this species is available. This study aimed to characterize the chemical composition of wild and cultured fish. The muscle proximate composition, and fatty acid and amino acid profiles were assessed. The cultivated specimens showed a higher lipid content and lower protein and ash contents compared with the wild specimens. The predominant tissue fatty acids in both the wild and cultivated fish were palmitic acid (16:0), oleic acid (18:1n-9) and docosahexaenoic acid (DHA, 22:6n-3). A higher content of arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (20:5n-3) and DHA were detected in the muscle of wild mullets, while the fish supplied with commercial pellets showed higher quantities of monounsaturated fatty acids, and lower quantities of saturated fatty acids and polyunsaturated fatty acids (PUFAs). Regarding PUFAs, n-3 fatty acids were predominant in wild mullets, while n-6 and n-9 were more abundant in farmed fish. In terms of amino acid composition, except for histidine in wild specimens, the amino acid amounts were higher than the FAO/WHO standard. In conclusion, C. labrosus may contribute to improving the dietary intake of highly polyunsaturated n-3 fatty acids, with a benefit to human health, owing to that fact that a 100-g fillet portion of cultivated and wild C. labrosus can provide 770 mg and 1160 mg of EPA and DHA, respectively, which exceeds the 250 mg dietary daily intake recommended by the FAO/WHO.

19.
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
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