RESUMEN
The common bed bug, Cimex lectularius, is an urban pest of global health significance, severely affecting the physical and mental health of humans. In contrast to most other blood-feeding arthropods, bed bugs are not major vectors of pathogens, but the underlying mechanisms for this phenomenon are largely unexplored. Here, we present the first transcriptomics study of bed bugs in response to immune challenges. To study transcriptional variations in bed bugs following ingestion of bacteria, we extracted and processed mRNA from body tissues of adult male bed bugs after ingestion of sterile blood or blood containing the Gram-positive (Gr+) bacterium Bacillus subtilis or the Gram-negative (Gr-) bacterium Escherichia coli. We analyzed mRNA from the bed bugs' midgut (the primary tissue involved in blood ingestion) and from the rest of their bodies (RoB; body minus head and midgut tissues). We show that the midgut exhibits a stronger immune response to ingestion of bacteria than the RoB, as indicated by the expression of genes encoding antimicrobial peptides (AMPs). Both the Toll and Imd signaling pathways, associated with immune responses, were highly activated by the ingestion of bacteria. Bacterial infection in bed bugs further provides evidence for metabolic reconfiguration and resource allocation in the bed bugs' midgut and RoB to promote production of AMPs. Our data suggest that infection with particular pathogens in bed bugs may be associated with altered metabolic pathways within the midgut and RoB that favors immune responses. We further show that multiple established cellular immune responses are preserved and are activated by the presence of specific pathogens. Our study provides a greater understanding of nuances in the immune responses of bed bugs towards pathogens that ultimately might contribute to novel bed bug control tactics.
Asunto(s)
Chinches , Perfilación de la Expresión Génica , Transcriptoma , Animales , Chinches/inmunología , Chinches/genética , Masculino , Escherichia coli/inmunología , Bacillus subtilis/inmunología , Bacillus subtilis/genética , Transducción de Señal/inmunología , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/inmunologíaRESUMEN
Insects rely only on their innate immune system to protect themselves from pathogens. Antimicrobial peptide (AMP) production is the main immune reaction in insects. In Drosophila melanogaster, the reaction is regulated mainly by the Toll and immune deficiency (IMD) pathways. Spaetzle proteins, activated by immune signals from upstream components, bind to Toll proteins, thus, activating the Toll pathway, which in turn, induces AMP genes. Previous studies have shown the difference in immune systems related to Toll and IMD pathways between D. melanogaster and Tribolium castaneum. In T. castaneum, nine Toll and seven spaetzle (spz) genes were identified. To extend our understanding of AMP production by T. castaneum, we conducted functional assays of Toll and spaetzle genes related to Toll-pathway-dependent AMP gene expression in T. castaneum under challenge with bacteria or budding yeast. The results revealed that Toll3 and Toll4 double-knockdown and spz7 knockdown strongly and moderately reduced the Toll-pathway-dependent expression of AMP genes, respectively. Moreover, Toll3 and Toll4 double-knockdown pupae more rapidly succumbed to entomopathogenic bacteria than the control pupae, but spz7 knockdown pupae did not. The results suggest that Toll3 and Toll4 play a large role in Toll-pathway-dependent immune reactions, whereas spz7 plays a small part.
Asunto(s)
Péptidos Antimicrobianos , Inmunidad Innata , Infecciones , Tribolium , Animales , Escarabajos/genética , Escarabajos/inmunología , Escarabajos/microbiología , Expresión Génica , Tribolium/genética , Tribolium/inmunología , Tribolium/microbiología , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/inmunología , Inmunidad Innata/inmunología , Infecciones/inmunología , Infecciones/microbiologíaRESUMEN
Alcohol use among older adults is on the rise. This increase is clinically relevant as older adults are at risk for increased morbidity and mortality from many alcohol-related chronic diseases compared to younger patients. However, little is known regarding the synergistic effects of alcohol and age. There are intriguing data suggesting that aging may lead to impaired intestinal barrier integrity and dysbiosis of the intestinal microbiome, which could increase susceptibility to alcohol's negative effects. To study the effects of alcohol in age we exposed aged and young mice to 3 days of moderate ethanol and evaluated changes in gut parameters. We found that these levels of drinking do not have obvious effects in young mice but cause significant alcohol-induced gut barrier dysfunction and expression of the pro-inflammatory cytokine TNFα in aged mice. Ethanol-induced downregulation of expression of the gut-protective antimicrobial peptides Defa-rs1, Reg3b, and Reg3g was observed in aged, but not young mice. Analysis of the fecal microbiome revealed age-associated shifts in microbial taxa, which correlated with intestinal and hepatic inflammatory gene expression. Taken together, these data demonstrate that age drives microbiome dysbiosis, while ethanol exposure in aged mice induces changes in the expression of antimicrobial genes important for separating these potentially damaging microbes from the intestinal lumen. These changes highlight potential mechanistic targets for prevention of the age-related exacerbation of effects of ethanol on the gut.
Asunto(s)
Disbiosis , Etanol , Microbioma Gastrointestinal , Inflamación , Intestinos , Animales , Ratones , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/inmunología , Citocinas/inmunología , Disbiosis/inducido químicamente , Disbiosis/genética , Disbiosis/inmunología , Disbiosis/microbiología , Etanol/farmacología , Etanol/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/inmunología , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/inmunología , Inflamación/microbiología , Intestinos/efectos de los fármacos , Intestinos/inmunología , Intestinos/microbiología , Ratones Endogámicos C57BL , Permeabilidad/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , alfa-Defensinas/genética , alfa-Defensinas/inmunologíaRESUMEN
Microbial resistance to antibiotics is an ancient and dynamic issue that has brought a situation reminiscent of the pre-antibiotic era to the limelight. Currently, antibiotic resistance and the associated infections are widespread and pose significant global health and economic burden. Thus, the misuse of antibiotics, which has increased resistance, has necessitated the search for alternative therapeutic agents for combating resistant pathogens. Antimicrobial peptides (AMPs) hold promise as a viable therapeutic approach against drug-resistant pathogens. AMPs are oligopeptides with low molecular weight. They have broad-spectrum antimicrobial activities against pathogenic microorganisms. AMPs are nonspecific and target components of microbes that facilitate immune response by acting as the first-line defense mechanisms against invading pathogenic microbes. The diversity and potency of AMPs make them good candidates for alternative use. They could be used alone or in combination with several other biomaterials for improved therapeutic activity. They can also be employed in vaccine production targeting drug-resistant pathogens. This review covers the opportunities and advances in AMP discovery and development targeting antimicrobial resistance (AMR) bacteria. Briefly, it presents an overview of the global burden of the antimicrobial resistance crisis, portraying the global magnitude, challenges, and consequences. After that, it critically and comprehensively evaluates the potential roles of AMPs in addressing the AMR crisis, highlighting the major potentials and prospects.
Asunto(s)
Antibacterianos , Péptidos Antimicrobianos , Farmacorresistencia Bacteriana , Inmunidad Innata , Humanos , Antibacterianos/inmunología , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Péptidos Antimicrobianos/inmunología , Péptidos Antimicrobianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/inmunología , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/inmunología , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/inmunología , Carga Global de Enfermedades , Descubrimiento de Drogas , Desarrollo de MedicamentosRESUMEN
The Drosophila Toll signaling pathway mainly responds to Gram-positive (G+) bacteria or fungal infection, which is highly conserved with mammalian TLR signaling pathway. Although many positive and negative regulators involved in the immune response of the Toll pathway have been identified in Drosophila, the roles of long noncoding RNAs (lncRNAs) in Drosophila Toll immune responses are poorly understood to date. In this study, our results demonstrate that lncRNA-CR33942 is mainly expressed in the nucleus and upregulated after Micrococcus luteus infection. Especially, lncRNA-CR33942 not only modulates differential expressions of multiple antimicrobial peptide genes but also affects the Drosophila survival rate during response to G+ bacterial infection based on the transiently overexpressing and the knockdown lncRNA-CR33942 assays in vivo. Mechanically, lncRNA-CR33942 interacts with the NF-κB transcription factors Dorsal-related immunity factor/Dorsal to promote the transcriptions of antimicrobial peptides drosomycin and metchnikowin, thus enhancing Drosophila Toll immune responses. Taken together, this study identifies lncRNA-CR33942 as a positive regulator of Drosophila innate immune response to G+ bacterial infection to facilitate Toll signaling via interacting with Dorsal-related immunity factor/Dorsal. It would be helpful to reveal the roles of lncRNAs in Toll immune response in Drosophila and provide insights into animal innate immunity.
Asunto(s)
Péptidos Antimicrobianos , Proteínas de Drosophila , Drosophila , ARN Largo no Codificante , Animales , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/inmunología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/inmunología , Drosophila/genética , Drosophila/inmunología , Proteínas de Drosophila/genética , Proteínas de Drosophila/inmunología , Drosophila melanogaster/genética , Drosophila melanogaster/inmunología , Inmunidad Innata/genética , Inmunidad Innata/inmunología , ARN Largo no Codificante/genética , ARN Largo no Codificante/inmunología , Factores de Transcripción/inmunología , Factores de Transcripción/metabolismoRESUMEN
Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes ß-defensin 2/defensin-ß4 (HBD2/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.
Asunto(s)
Péptidos Antimicrobianos/inmunología , Antivirales/inmunología , COVID-19/inmunología , Inmunidad Innata/inmunología , SARS-CoV-2/inmunología , Vitamina D/análogos & derivados , Péptidos Catiónicos Antimicrobianos/sangre , Péptidos Catiónicos Antimicrobianos/inmunología , Péptidos Antimicrobianos/sangre , Calcitriol/sangre , Calcitriol/inmunología , Catelicidinas/sangre , Catelicidinas/inmunología , Humanos , Receptores de Calcitriol/sangre , Receptores de Calcitriol/inmunología , Transducción de Señal/inmunología , Vitamina D/sangre , Vitamina D/inmunología , Deficiencia de Vitamina D/inmunología , Deficiencia de Vitamina D/virología , beta-Defensinas/sangre , beta-Defensinas/inmunologíaRESUMEN
Micropterus salmoides is an economical important species of freshwater-cultured fish, the in-depth knowledge of its immune system is in urgent development to cope with serious infectious diseases. Piscidin is an important antimicrobial peptide (AMP) family existing in almost all teleosts. However, no piscidin has been reported in largemouth bass. In this study, three novel piscidins (MSPiscidin-1, -2, and -3) were firstly identified and characterized from the largemouth bass. The predicted mature peptides of MSPiscidin-1, -2, and -3 (consists of 24, 27, 25 amino acid residues, respectively) all adopted an amphipathic α-helical conformation representative of cationic AMPs that are important for membrane permeabilization and antibacterial activity. MSPiscidin-2 and -3 indeed displayed strong, broad-spectrum, and highly efficient antimicrobial activities in vitro against aquatic pathogens, but MSPiscidin-1 didn't show direct antimicrobial activity. MSPiscidin-2 and -3 killed bacteria mainly by inducing membrane permeabilization, in addition, they also can interact with bacterial genomic DNA, which might influence the DNA replication and transcription. Besides, MSPiscidin-2 and -3 could effectively inhibit the formation of the bacterial biofilm and eliminate the preformed biofilms. In vivo, MSPiscidin-1-3 genes showed an inducible expression pattern in the tested tissues upon Vibrio harveyi infection, which further indicated the key roles of piscidins in innate immunity in largemouth bass. Overall, this study will supplement the understanding of M. salmoides innate immune system and provide candidates for the design of novel peptide antibacterial agents used in aquaculture.
Asunto(s)
Péptidos Antimicrobianos/inmunología , Lubina , Proteínas de Peces/inmunología , Animales , Lubina/inmunología , Lubina/microbiología , Agua Dulce , Inmunidad InnataRESUMEN
Before eliciting an adaptive immune response, SARS-CoV-2 must overcome seven constitutive respiratory defense barriers. The first is the mucus covering the respiratory tract's luminal surface, which entraps inhaled particles, including infectious agents, and eliminates them by mucociliary clearance. The second barrier comprises various components present in the airway lining fluid, the surfactants. Besides providing low surface tension that allows efficient gas exchange at the alveoli, surfactants inhibit the invasion of epithelial cells by respiratory viruses, enhance pathogen uptake by phagocytes, and regulate immune cells' functions. The respiratory tract microbiota constitutes the third defense barrier against SARS-CoV-2. It activates the innate and adaptive immune cells and elicits anti-infectious molecules such as secretory IgA antibodies, defensins, and interferons. The fourth defense barrier comprises the antimicrobial peptides defensins, and lactoferrin. They show direct antiviral activity, inhibit viral fusion, and modulate the innate and adaptive immune responses. Secretory IgA antibodies, the fifth defense barrier, besides protecting the local microbiota against noxious agents, also inhibit SARS-CoV-2 cell invasion. If the virus overcomes this barrier, it reaches its target, the respiratory epithelial cells. However, these cells also act as a defense barrier, the sixth one, since they hinder the virus' access to receptors and produce antiviral and immunomodulatory molecules such as interferons, lactoferrin, and defensins. Finally, the sensing of the virus by the cells of innate immunity, the last constitutive defense barrier, elicits a cascade of signals that activate adaptive immune cells and may inhibit the development of productive infection. The subject of the present essay is discussing these mechanisms.
Asunto(s)
COVID-19 , Inmunidad Innata , Anticuerpos Antivirales/inmunología , Péptidos Antimicrobianos/inmunología , COVID-19/inmunología , Humanos , Inmunoglobulina A/inmunología , Interferones/inmunología , Pulmón/inmunología , Pulmón/virología , SARS-CoV-2RESUMEN
CpG-oligodeoxynucleotides (CpG-ODNs) constitute an attractive alternative for asthma treatment. However, very little evidence is available from studies on the oral administration of CpG-ODNs in animals. Previously, we developed acid-resistant particles (named ODNcap) as an oral delivery device for ODNs. Here, we showed that free feeding of an ODNcap-containing feed prophylactically attenuates allergic airway inflammation, hyperresponsiveness, and goblet cell hyperplasia in an ovalbumin-induced asthma model. Using transcriptomics-driven approaches, we demonstrated that injury of pulmonary vein cardiomyocytes accompanies allergen inhalation challenge, but is inhibited by ODNcap feeding. We also showed the participation of an airway antimicrobial peptide (Reg3γ) and fecal microbiota in the ODNcap-mediated effects. Collectively, our findings suggest that daily oral ingestion of ODNcap may provide preventive effects on allergic bronchopulmonary insults via regulation of mechanisms involved in the gut-lung connection.
Asunto(s)
Hiperreactividad Bronquial/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Hipersensibilidad/inmunología , Oligodesoxirribonucleótidos/farmacología , Neumonía/inmunología , Administración Oral , Animales , Péptidos Antimicrobianos/inmunología , Femenino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Ovalbúmina/toxicidad , Proteínas Asociadas a Pancreatitis/inmunologíaRESUMEN
Evidence of immune memory in invertebrates (immune priming) has accumulated in various organisms, and both cellular and humoral immune reactions are speculated to be involved in immune priming. However, there is a lack of understanding of the molecular mechanisms involved. In the present study, the protective effect of primed haemolymph was further validated by the increased survival rate of naïve crabs receiving a transfusion of primed haemolymph. By proteomic analysis, there were 474 proteins identified from the primed haemolymph, and most of them were functionally annotated in transport and metabolism classes. A total of 70 proteins were found to be differentially expressed in haemolymph at 12 hours and 7 days after priming stimulation with Aeromonas hydrophila, among which anti-lipopolysaccharide factor 1 (EsALF-1) and 3 (EsALF-3) were identified as the most significant (p < 0.05). After being challenged with A. hydrophila, EsALF-1 and EsALF-3 were highly expressed at both mRNA (in haemocytes) and protein (in haemolymph) levels compared with blank crabs, and the mRNA expressions of components in the EsTLR1-EsMyd88-EsPelle-EsALF pathway also increased significantly (p < 0.05). The EsALF-3 and EsMyd88 were even significantly higher expressed in response to the second A. hydrophila challenge, but their expressions all decreased (p < 0.05) when EsTLR1 was knocked down by RNAi. After the naïve crabs received an injection with the recombinant protein of EsALF-1 (rEsALF-1) or EsALF-3 (rEsALF-3), their survival rate increased significantly (p < 0.05) upon A. hydrophila stimulation. In contrast, the survival rate of the primed crabs reduced significantly (p < 0.05) after they received an injection with the antibody of EsALF-1 or EsALF-3. The enhanced expressions of EsALF-1 and EsALF-3 after A. hydrophilap riming stimulation could sustain for four weeks. All the results suggested that the EsTLR1-mediated productions of EsALF-1 and EsALF-3 in haemolymph played an indispensable role in the month-long humoral immune protection induced by A. hydrophila, which provides solid evidence of immune priming in crabs and a valuable reference for further understanding immune memory in invertebrates.
Asunto(s)
Aeromonas hydrophila/inmunología , Péptidos Antimicrobianos/biosíntesis , Proteínas de Artrópodos/biosíntesis , Braquiuros/inmunología , Lipopolisacáridos/toxicidad , Anciano , Animales , Especificidad de Anticuerpos , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/inmunología , Acuicultura , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Braquiuros/genética , Braquiuros/microbiología , Clonación Molecular , Femenino , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Hemocitos/metabolismo , Hemolinfa/inmunología , Humanos , Inmunidad Humoral , Ratones , Proteómica , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Receptores Toll-Like/fisiologíaRESUMEN
Although class B scavenger receptors (SR-Bs) in mammals are multifunctional molecules, the functions of SR-Bs in invertebrates remain largely unknown. In this study, we characterized an SR-B homolog, namely SpSR-B2, from Scylla paramamosain. SpSR-B2 shared high similarity with mammalian SR-Bs, and exhibited specific binding activity to ac-LDL, indicating that it may be a new member of SR-B class in invertebrates. SpSR-B2 was upregulated after challenge with white spot syndrome virus (WSSV) or bacteria. Binding assays showed that SpSR-B2 specifically interacted with WSSV envelope protein VP24. Besides, SpSR-B2 could bind to all tested bacterial cells and agglutinate these bacteria. SpSR-B2 also exhibited a strong binding activity to LPS but weak binding activities to other tested polysaccharides. These findings indicated that SpSR-B2 was a potential recognition molecule for viral protein VP24 and bacterial LPS. Knockdown of SpSR-B2 resulted in dramatically decreased expressions of certain antimicrobial peptides (AMPs), and overexpression of SpSR-B2 led to the increased expression of the AMP of SpALF2, suggesting that SpSR-B2 could regulate the expression of AMPs. Taken together, this study revealed that SpSR-B2 functioned as a potential pattern recognition receptor participating in antiviral and antibacterial immunity, and provided new insights into the immune functions of invertebrate SR-Bs.
Asunto(s)
Antibacterianos/inmunología , Antivirales/inmunología , Proteínas de Artrópodos/inmunología , Braquiuros/inmunología , Receptores de Reconocimiento de Patrones/inmunología , Animales , Péptidos Antimicrobianos/inmunología , Bacterias/inmunología , Inmunidad/inmunología , Lipopolisacáridos/inmunología , Filogenia , Virus del Síndrome de la Mancha Blanca 1/inmunologíaRESUMEN
In animals, immune signaling pathways and effector molecules participate in attenuating microbial infection. Recent work has shown that the Nimrod family proteins can directly bind to bacteria, and this binding leads to bacterial phagocytosis. Although the Nimrod gene family has been reported in many non-drosophilids, their functions remain unexplored in most insect species. Here, we report two members (Nimrod-B and Draper) of the Nimrod gene family from Bombyx mori and analyzed their role in immunity. The two genes were ubiquitously expressed in the tested tissues; but, they transcribed preferentially in immune tissues. The developmental profiles showed that BmNimrod-B and BmDraper transcription levels were highest in the pupal stages. Challenge with microbial pathogens induced the transcription levels of all two genes at different time points. Knockdown of BmDraper decreased the bacterial clearance and increased their replication relative to the control group, whereas, BmNimrod-B suppression had a non-significant effect on them. Furthermore, the mortality rate was increased after BmDraper silencing. The knockdown of these genes did not significantly affect the production of antimicrobial peptides following E. coli infection. Taken together, the Nimrod family genes play a crucial role in host defense by positively regulating the antibacterial immune response in silkworm B. mori.
Asunto(s)
Péptidos Antimicrobianos/inmunología , Bombyx/metabolismo , Infecciones por Escherichia coli/inmunología , Proteínas de Insectos/inmunología , Mesilatos/inmunología , AnimalesRESUMEN
Unlike almost all hematophagous insects, common bed bugs, Cimex lectularius, are not known to transmit pathogens to humans. To help unravel the reasons for their lack of vector competence, we studied the time- and tissue-dependent expression of innate immune factors after blood feeding or immune activation through the intrathoracic injection of bacteria. We used minimum inhibitory concentration (MIC1) bioassays and the Kirby-Bauer protocol to evaluate antimicrobial peptide (AMP2) activity in tissue extracts from the midguts or 'rest of body' (RoB3) tissues (containing hemolymph and fat body AMPs) against Gram-positive and Gram-negative bacteria. We compared AMP activity between blood-fed female bed bugs and yellow fever mosquitoes, Aedes aegypti and determined how female and male bed bugs respond to immune challenges, and how long AMP gene expression remains elevated in bed bugs following a blood meal. Blood meal-induced AMP activity is 4-fold stronger in female bed bugs than in female mosquitoes. Male bed bugs have elevated AMP activity within 8 h of a blood meal or an intrathoracic injection with bacteria, with the strongest activity expressed in RoB tissue 24 h after the immune challenge. Female bed bugs have a stronger immune response than males within 24 h of a blood meal. The effects of blood meal-induced elevated AMP activity lasts longer against the Gram-positive bacterium, Bacillus subtilis, than against the Gram-negative bacterium Escherichia coli. Unravelling the specific immune pathways that are activated in the bed bugs' immune responses and identifying the bed bug-unique AMPs might help determine why these insects are not vectors of human parasites.
Asunto(s)
Péptidos Antimicrobianos/inmunología , Chinches , Aedes , Animales , Chinches/inmunología , Chinches/microbiología , Cuerpo Adiposo/inmunología , Conducta Alimentaria , Femenino , Bacterias Gramnegativas , Bacterias Grampositivas , Hemolinfa/inmunología , Masculino , Factores de TiempoRESUMEN
Porcine epidemic diarrhea virus (PEDV) is emerging as a major threat to the global swine industry. Clinical PEDV infection is associated with severe intestinal lesions, resulting in absorptive dysfunction and high mortality rates in suckling piglets. The extracellular matrix (ECM) is an important component of intestinal tissue, providing a structural framework and conveying tissue-specific signals to nearby enterocytes. In this study, we investigated the extensive ECM remodeling observed in intestinal epithelial cells infected with PEDV and elucidated the associated activated ECM receptor-related pathways. Protein-protein interaction network analysis revealed two significantly differentially expressed genes (cluster of differentiation 44 [CD44] and serpin family E member 1 [SERPINE1]) associated with the ECM. At the transcriptional level, both genes exhibited significant positive correlation with the extent of PEDV replication. Similarly, the expression of CD44 and PAI-1 (encoded by SERPINE1) was also increased in the intestines of piglets during viral infection. Furthermore, CD44 exhibited antiviral activity by enhancing the expression of antiviral cytokines (e.g., interleukin [IL]-6, IL-18, IL-11, and antimicrobial peptide beta-defensin 1) by activating nuclear factor-κB signaling. Conversely, PAI-1 was found to promote the release of progeny virions during PEDV infection, despite a decreased intracellular viral load. Nevertheless, the underlying mechanisms are still unclear. Taken together, our results highlighted the biological roles of specific ECM-regulated genes, i.e., CD44 and SERPINE1 in suppressing and promoting PEDV infection, thereby providing a theoretical foundation for the role of the ECM in intestinal infections and identifying potential therapeutic targets for PEDV.
Asunto(s)
Infecciones por Coronavirus , Matriz Extracelular , Transducción de Señal , Enfermedades de los Porcinos , Animales , Péptidos Antimicrobianos/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/veterinaria , Receptores de Hialuranos/inmunología , Intestinos/virología , Inhibidor 1 de Activador Plasminogénico/inmunología , Virus de la Diarrea Epidémica Porcina , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/virologíaRESUMEN
The innate immune system of human skin consists of a multi-layered barrier consisting of cells and soluble effector molecules charged with maintaining homeostasis and responding to insults and infections. It has become increasingly clear that these barrier layers become compromised in skin diseases, especially in disorders of an (auto)inflammatory nature. In the case of hidradenitis suppurativa, great strides have been made in recent years in characterizing the underlying breakdown in homeostatic innate immunity, including an increasing understanding of the central role of the hair follicle in this process. This breakdown appears to occur at multiple levels: the pilosebaceous unit, associated epithelium, the cutaneous microbiome, alteration of immune cell function and local molecular events such as complement activation. This review seeks to summarize, contextualize and analyse critically our current understanding of how these innate immune barriers become dysregulated in the early stage(s) of hidradenitis suppurativa, and to speculate on where potential hidradenitis suppurativa research could be most fruitful.
Asunto(s)
Hidradenitis Supurativa/inmunología , Inmunidad Innata/inmunología , Microbiota/inmunología , Péptidos Antimicrobianos/inmunología , HumanosRESUMEN
Gut microbiota is a constant source of antigens and stimuli to which the resident immune system has developed tolerance. However, the mechanisms by which mononuclear phagocytes, specifically monocytes/macrophages, cope with these usually pro-inflammatory signals are poorly understood. Here, we show that innate immune memory promotes anti-inflammatory homeostasis, using as model strains of the commensal bacterium Lactiplantibacillus plantarum. Priming of monocytes/macrophages with bacteria, especially in its live form, enhances bacterial intracellular survival and decreases the release of pro-inflammatory signals to the environment, with lower production of TNF and higher levels of IL-10. Analysis of the transcriptomic landscape of these cells shows downregulation of pathways associated with the production of reactive oxygen species (ROS) and the release of cytokines, chemokines and antimicrobial peptides. Indeed, the induction of ROS prevents memory-induced bacterial survival. In addition, there is a dysregulation in gene expression of several metabolic pathways leading to decreased glycolytic and respiratory rates in memory cells. These data support commensal microbe-specific metabolic changes in innate immune memory cells that might contribute to homeostasis in the gut.
Asunto(s)
Inmunidad Innata , Lactobacillaceae/inmunología , Macrófagos/inmunología , Monocitos/inmunología , Adulto , Anciano , Animales , Péptidos Antimicrobianos/inmunología , Femenino , Humanos , Memoria Inmunológica , Interleucina-10/inmunología , Macrófagos/microbiología , Masculino , Ratones , Microbiota , Persona de Mediana Edad , Monocitos/microbiología , Células RAW 264.7 , Saliva/microbiología , SimbiosisRESUMEN
The gut microbiota affects the physiology and metabolism of animals and its alteration can lead to diseases such as gut dysplasia or metabolic disorders. Several reports have shown that the immune system plays an important role in shaping both bacterial community composition and abundance in Drosophila, and that immune deficit, especially during aging, negatively affects microbiota richness and diversity. However, there has been little study at the effector level to demonstrate how immune pathways regulate the microbiota. A key set of Drosophila immune effectors are the antimicrobial peptides (AMPs), which confer defense upon systemic infection. AMPs and lysozymes, a group of digestive enzymes with antimicrobial properties, are expressed in the gut and are good candidates for microbiota regulation. Here, we take advantage of the model organism Drosophila melanogaster to investigate the role of AMPs and lysozymes in regulation of gut microbiota structure and diversity. Using flies lacking AMPs and newly generated lysozyme mutants, we colonized gnotobiotic flies with a defined set of commensal bacteria and analyzed changes in microbiota composition and abundance in vertical transmission and aging contexts through 16S rRNA gene amplicon sequencing. Our study shows that AMPs and, to a lesser extent, lysozymes are necessary to regulate the total and relative abundance of bacteria in the gut microbiota. We also decouple the direct function of AMPs from the immune deficiency (IMD) signaling pathway that regulates AMPs but also many other processes, more narrowly defining the role of these effectors in the microbial dysbiosis observed in IMD-deficient flies upon aging. IMPORTANCE This study advances current knowledge in the field of host-microbe interactions by demonstrating that the two families of immune effectors, antimicrobial peptides and lysozymes, actively regulate the gut microbiota composition and abundance. Consequences of the loss of these antimicrobial peptides and lysozymes are exacerbated during aging, and their loss contributes to increased microbiota abundance and shifted composition in old flies. This work shows that immune effectors, typically associated with resistance to pathogenic infections, also help shape the beneficial gut community, consistent with the idea that host-symbiont interactions use the same "language" typically associated with pathogenesis.
Asunto(s)
Péptidos Antimicrobianos/metabolismo , Drosophila melanogaster/química , Drosophila melanogaster/microbiología , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiología , Muramidasa/metabolismo , Animales , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/inmunología , Bacterias/clasificación , Bacterias/genética , Drosophila melanogaster/genética , Drosophila melanogaster/inmunología , Femenino , Microbioma Gastrointestinal/inmunología , Interacciones Microbiota-Huesped , Sistema Inmunológico , Muramidasa/genética , Muramidasa/inmunología , ARN Ribosómico 16S/genética , SimbiosisRESUMEN
The skin microbiome plays an important role in maintaining skin homeostasis by controlling inflammation, providing immune education and maintaining host defense. However, in many inflammatory skin disorders the skin microbiome is disrupted. This dysbiotic community may contribute to disease initiation or exacerbation through the induction of aberrant immune responses in the absence of infection. Hidradenitis suppurativa (HS) is a complex, multifaceted disease involving the skin, innate and adaptive immunity, microbiota and environmental stimuli. Herein, we discuss the current state of HS skin microbiome research and how microbiome components may activate pattern recognition receptor (PRR) pathways, metabolite sensing pathways and antigenic receptors to drive antimicrobial peptide, cytokine, miRNA and adaptive immune cell responses in HS. We highlight the major open questions that remain to be addressed and how antibiotic therapies for HS likely influence both microbial burden and inflammation. Ultimately, we hypothesize that the two-way communication between the skin microbiome and host immune response in HS skin generates a chronic positive feed-forward loop that perpetuates chronic inflammation, tissue destruction and disease exacerbation.
Asunto(s)
Hidradenitis Supurativa/inmunología , Hidradenitis Supurativa/microbiología , Inmunidad , Microbiota , Piel/inmunología , Piel/microbiología , Péptidos Antimicrobianos/inmunología , Disbiosis/inmunología , Disbiosis/microbiología , HumanosRESUMEN
Insects possess an immune system that protects them from attacks by various pathogenic microorganisms that would otherwise threaten their survival. Immune mechanisms may deal directly with the pathogens by eliminating them from the host organism or disarm them by suppressing the synthesis of toxins and virulence factors that promote the invasion and destructive action of the intruder within the host. Insects have been established as outstanding models for studying immune system regulation because innate immunity can be explored as an integrated system at the level of the whole organism. Innate immunity in insects consists of basal immunity that controls the constitutive synthesis of effector molecules such as antimicrobial peptides, and inducible immunity that is activated after detection of a microbe or its product(s). Activation and coordination of innate immune defenses in insects involve evolutionary conserved immune factors. Previous research in insects has led to the identification and characterization of distinct immune signalling pathways that modulate the response to microbial infections. This work has not only advanced the field of insect immunology, but it has also rekindled interest in the innate immune system of mammals. Here we review the current knowledge on key molecular components of insect immunity and discuss the opportunities they present for confronting infectious diseases in humans.