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1.
J Insect Sci ; 21(1)2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33560363

RESUMEN

Insect innate immunity is initiated by the special recognition and binding of the foreign pathogens, which is accomplished by the pattern recognition receptors (PRRs). As an important type of PRRs, C-type lectins (CTLs) play various roles in insect innate immunity, including pathogen recognition, stimulation of prophenoloxidase, regulation of cellular immunity and so on. In this study, we have cloned the full-length cDNA of a CTL gene named CTL-S6 from the silkworm, Bombyx mori. The open reading frame (ORF) of B. mori CTL-S6 encodes 378 amino acids, which contain a secretion signal peptide. The mRNA of CTL-S6 exhibited the highest transcriptional level in the midgut. Its transcriptional level increased dramatically in fat body and hemocytes upon Escherichia coli or Micrococcus luteus challenge. Purified recombinant CTL-S6 could bind to bacterial cell wall components, including peptidoglycan (PGN, from Bacillus subtilis) and lipopolysaccharide (LPS, from E. coli 0111:B4), and recombinant CTL-S6 was involved in the encapsulation and melanization of hemocytes. Furthermore, the addition of recombinant CTL-S6 to the hemolymph of silkworm resulted in a significant increase in phenoloxidase activity. Overall, our results indicated that B. mori CTL-S6 may serve as a PRR for the recognition of foreign pathogens, prophenoloxidase pathway stimulation and involvement in the innate immunity.


Asunto(s)
Bombyx/genética , Bombyx/inmunología , Inmunidad Innata , Proteínas de Insectos/genética , Lectinas Tipo C/genética , Secuencia de Aminoácidos , Animales , Bombyx/crecimiento & desarrollo , Escherichia coli/fisiología , Cuerpo Adiposo/inmunología , Hemocitos/inmunología , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Larva/genética , Larva/crecimiento & desarrollo , Larva/inmunología , Lectinas Tipo C/química , Lectinas Tipo C/metabolismo , Micrococcus luteus/fisiología , Filogenia , Alineación de Secuencia
2.
Cell Rep ; 34(7): 108761, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33567255

RESUMEN

Coronavirus disease 2019 (COVID-19) is a current global health threat caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that SARS-CoV-2 elicits a dysregulated immune response and a delayed interferon (IFN) expression in patients, which contribute largely to the viral pathogenesis and development of COVID-19. However, underlying mechanisms remain to be elucidated. Here, we report the activation and repression of the innate immune response by SARS-CoV-2. We show that SARS-CoV-2 RNA activates the RIG-I-MAVS-dependent IFN signaling pathway. We further uncover that ORF9b immediately accumulates and antagonizes the antiviral type I IFN response during SARS-CoV-2 infection on primary human pulmonary alveolar epithelial cells. ORF9b targets the nuclear factor κB (NF-κB) essential modulator NEMO and interrupts its K63-linked polyubiquitination upon viral stimulation, thereby inhibiting the canonical IκB kinase alpha (IKKα)/ß/γ-NF-κB signaling and subsequent IFN production. Our findings thus unveil the innate immunosuppression by ORF9b and provide insights into the host-virus interplay during the early stage of SARS-CoV-2 infection.


Asunto(s)
/genética , Quinasa I-kappa B/metabolismo , /metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/virología , /metabolismo , Células HEK293 , Humanos , Inmunidad Innata/inmunología , Interferón Tipo I/metabolismo , Interferones/metabolismo , FN-kappa B/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Cultivo Primario de Células , Receptores de Ácido Retinoico/metabolismo , /inmunología , Transducción de Señal , Ubiquitinación
3.
Curr Top Microbiol Immunol ; 431: 233-263, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33620654

RESUMEN

Human infections with the food-borne pathogen Campylobacter jejuni are progressively increasing worldwide and constitute a significant socioeconomic burden to mankind. Intestinal campylobacteriosis in humans is characterized by bloody diarrhea, fever, abdominal pain, and severe malaise. Some individuals develop chronic post-infectious sequelae including neurological and autoimmune diseases such as reactive arthritis and Guillain-Barré syndrome. Studies unraveling the molecular mechanisms underlying campylobacteriosis and post-infectious sequelae have been hampered by the scarcity of appropriate experimental in vivo models. Particularly, conventional laboratory mice are protected from C. jejuni infection due to the physiological colonization resistance exerted by the murine gut microbiota composition. Additionally, as compared to humans, mice are up to 10,000 times more resistant to C. jejuni lipooligosaccharide (LOS) constituting a major pathogenicity factor responsible for the immunopathological host responses during campylobacteriosis. In this chapter, we summarize the recent progress that has been made in overcoming these fundamental obstacles in Campylobacter research in mice. Modification of the murine host-specific gut microbiota composition and sensitization of the mice to C. jejuni LOS by deletion of genes encoding interleukin-10 or a single IL-1 receptor-related molecule as well as by dietary zinc depletion have yielded reliable murine infection models resembling key features of human campylobacteriosis. These substantial improvements pave the way for a better understanding of the molecular mechanisms underlying pathogen-host interactions. The ongoing validation and standardization of these novel murine infection models will provide the basis for the development of innovative treatment and prevention strategies to combat human campylobacteriosis and collateral damages of C. jejuni infections.


Asunto(s)
Infecciones por Campylobacter , Campylobacter jejuni , Animales , Modelos Animales de Enfermedad , Inmunidad Innata , Ratones , Ratones Endogámicos C57BL
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(2): 256-263, 2021 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-33624600

RESUMEN

OBJECTIVE: To explore the effect of Huangqin decoction (HQD) on group 3 innate lymphoid cells (ILC3s) and helper T cells (Th) for treatment of ulcerative colitis (UC). OBJECTIVE: Male Balb/c mice were randomly divided into control group, DSS group, mesalazine group (ME, 400 mg/kg), and 2.275 g/kg, 4.55 g/kg and 9.1 g/kg HQD groups. All the mice were given free access to normal chow. Except for those in the normal control group, all the mice were given 3% DSS solution for 7 days to establish models of UC. The mice in ME group and 3 HQD groups were given mesalazine or HQD via oral gavage at the specified doses once a day. Flow cytometry was performed to analyze the ILC3s, MHC Ⅱ, Th1 and Treg in the lamina propria lymphocytes in the colon. Milliplex was performed to determine cytokine levels of in the colon tissues. OBJECTIVE: Compared with those in DSS group, the mice in the 3 HQD groups all showed obviously lessened symptoms of UC with significantl decreased DAI score (P < 0.001) and macroscopic score (P < 0.001). The results of flow cytometry showed that HQD treatment significantly increased the percentage of ILC3s (P < 0.05) and expression of MHCⅡ (P < 0.05), obviously reduced the proportion of Th1 (P < 0.05) but increased Treg cells (P < 0.05) in the colon tissues. Milliplex showed that HQD treatment significantly reduced the expressions of Th-related pro-inflammatory cytokines including IL-2 (P < 0.05), IL-17A (P < 0.05), IL-23 (P < 0.05), TNF-α (P < 0.05), and IFN-γ (P < 0.05). OBJECTIVE: HQD alleviates DSS- induced UC in mice by increasing ILC3s and MHC Ⅱ expression to suppress the function of Th17 and Th1 cells and promote Treg and Th2 cells.


Asunto(s)
Colitis Ulcerosa , Animales , Recuento de Células , Colitis Ulcerosa/tratamiento farmacológico , Inmunidad Innata , Masculino , Mesalamina/uso terapéutico , Ratones , Scutellaria baicalensis
5.
Mol Med Rep ; 23(4): 1, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33576464

RESUMEN

Recently, severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS­CoV­2)­causing CoV disease 2019 (COVID­19) emerged in China and has become a global pandemic. SARS­CoV­2 is a novel CoV originating from ß­CoVs. Major distinctions in the gene sequences between SARS­CoV and SARS­CoV­2 include the spike gene, open reading frame (ORF) 3b and ORF 8. SARS­CoV­2 infection is initiated when the virus interacts with angiotensin­converting enzyme 2 (ACE2) receptors on host cells. Through this mechanism, the virus infects the alveolar, esophageal epithelial, ileum, colon and other cells on which ACE2 is highly expressed, causing damage to target organs. To date, host innate immunity may be the only identified direct factor associated with viral replication. However, increased ACE2 expression may upregulate the viral load indirectly by increasing the baseline level of infectious virus particles. The peak viral load of SARS­CoV­2 is estimated to occur ~10 days following fever onset, causing patients in the acute stage to be the primary infection source. However, patients in the recovery stage or with occult infections can also be contagious. The host immune response in patients with COVID­19 remains to be elucidated. By studying other SARS and Middle East respiratory syndrome coronaviruses, it is hypothesized that patients with COVID­19 may lack sufficient antiviral T­cell responses, which consequently present with innate immune response disorders. This may to a certain degree explain why this type of CoV triggers severe inflammatory responses and immune damage and its associated complications.


Asunto(s)
/patología , /fisiología , Inmunidad Adaptativa , /inmunología , Humanos , Inmunidad Innata , /inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Carga Viral
6.
Nat Commun ; 12(1): 1112, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33602937

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNα and IFNλ levels when compared to non-severe COVID-19 patients. In a mouse model of pulmonary HSV-1 infection, treatment with recombinant IL-3 reduces viral load and mortality. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating pDCs into the airways by stimulating CXCL12 secretion from pulmonary CD123+ epithelial cells, both, in mice and in COVID-19 negative patients exhibiting pulmonary diseases. This study identifies IL-3 as a predictive disease marker for SARS-CoV-2 infections and as a potential therapeutic target for pulmunory viral infections.


Asunto(s)
/diagnóstico , Interleucina-3/sangre , Animales , Quimiocina CXCL12/inmunología , Células Dendríticas/citología , Modelos Animales de Enfermedad , Femenino , Alemania , Humanos , Inmunidad Innata , Interferones/sangre , Pulmón/inmunología , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Linfocitos T/citología , Carga Viral
7.
Pathog Dis ; 79(1)2021 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-33537740

RESUMEN

A vast proportion of coronavirus disease 2019 (COVID-19) individuals remain asymptomatic and can shed severe acute respiratory syndrome (SARS-CoV) type 2 virus to transmit the infection, which also explains the exponential increase in the number of COVID-19 cases globally. Furthermore, the rate of recovery from clinical COVID-19 in certain pockets of the globe is surprisingly high. Based on published reports and available literature, here, we speculated a few immunovirological mechanisms as to why a vast majority of individuals remain asymptomatic similar to exotic animal (bats and pangolins) reservoirs that remain refractile to disease development despite carrying a huge load of diverse insidious viral species, and whether such evolutionary advantage would unveil therapeutic strategies against COVID-19 infection in humans. Understanding the unique mechanisms that exotic animal species employ to achieve viral control, as well as inflammatory regulation, appears to hold key clues to the development of therapeutic versatility against COVID-19.


Asunto(s)
Animales Exóticos/virología , /virología , Reservorios de Enfermedades/virología , Inmunidad Innata/inmunología , /inmunología , Animales , Infecciones Asintomáticas , Quirópteros/virología , Humanos , /virología
8.
Blood Adv ; 5(3): 913-925, 2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33560402

RESUMEN

Tyrosine kinase inhibitors (TKIs) are used to target dysregulated signaling pathways in virtually all hematologic malignancies. Many of the targeted signaling pathways are also essential in nonmalignant immune cells. The current coronavirus severe acute respiratory syndrome coronavirus 2 pandemic catalyzed clinical exploration of TKIs in the treatment of the various stages of COVID-19, which are characterized by distinct immune-related complications. Most of the reported effects of TKIs on immune regulation have been explored in vitro, with different class-specific drugs having nonoverlapping target affinities. Moreover, many of the reported in vivo effects are based on artificial animal models or on observations made in symptomatic patients with a hematologic malignancy who often already suffer from disturbed immune regulation. Based on in vitro and clinical observations, we attempt to decipher the impact of the main TKIs approved or in late-stage development for the treatment of hematological malignancies, including inhibitors of Bruton's tyrosine kinase, spleen tyrosine kinase, BCR-Abl, phosphatidylinositol 3-kinase/ mammalian target of rapamycin, JAK/STAT, and FMS-like tyrosine kinase 3, to provide a rationale for how such inhibitors could modify clinical courses of diseases, such as COVID-19.


Asunto(s)
Inmunidad Adaptativa , Neoplasias Hematológicas/tratamiento farmacológico , Inmunidad Innata , Inhibidores de Proteínas Quinasas/uso terapéutico , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Agammaglobulinemia Tirosina Quinasa/metabolismo , /inmunología , Citocinas/metabolismo , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Proteínas de Fusión bcr-abl/metabolismo , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/patología , Humanos , /aislamiento & purificación
9.
Viruses ; 13(2)2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-33530371

RESUMEN

Viral dysregulation or suppression of innate immune responses is a key determinant of virus-induced pathogenesis. Important sensors for the detection of virus infection are the RIG-I-like receptors (RLRs), which, in turn, are antagonized by many RNA viruses and DNA viruses. Among the different escape strategies are viral mechanisms to dysregulate the post-translational modifications (PTMs) that play pivotal roles in RLR regulation. In this review, we present the current knowledge of immune evasion by viral pathogens that manipulate ubiquitin- or ISG15-dependent mechanisms of RLR activation. Key viral strategies to evade RLR signaling include direct targeting of ubiquitin E3 ligases, active deubiquitination using viral deubiquitinating enzymes (DUBs), and the upregulation of cellular DUBs that regulate RLR signaling. Additionally, we summarize emerging new evidence that shows that enzymes of certain coronaviruses such as SARS-CoV-2, the causative agent of the current COVID-19 pandemic, actively deISGylate key molecules in the RLR pathway to escape type I interferon (IFN)-mediated antiviral responses. Finally, we discuss the possibility of targeting virally-encoded proteins that manipulate ubiquitin- or ISG15-mediated innate immune responses for the development of new antivirals and vaccines.


Asunto(s)
Citocinas/metabolismo , Proteína 58 DEAD Box/metabolismo , Evasión Inmune , Ubiquitina/metabolismo , Ubiquitinas/metabolismo , Virus/inmunología , /antagonistas & inhibidores , Humanos , Inmunidad Innata , /metabolismo , Transducción de Señal , Virosis/inmunología , Virosis/metabolismo , Virosis/virología , Virus/metabolismo
10.
Nat Commun ; 12(1): 793, 2021 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-33542240

RESUMEN

Adenosine-to-inosine (A-to-I) editing of eukaryotic cellular RNAs is essential for protection against auto-immune disorders. Editing is carried out by ADAR1, whose innate immune response-specific cytoplasmic isoform possesses a Z-DNA binding domain (Zα) of unknown function. Zα also binds to CpG repeats in RNA, which are a hallmark of Z-RNA formation. Unexpectedly, Zα has been predicted - and in some cases even shown - to bind to specific regions within mRNA and rRNA devoid of such repeats. Here, we use NMR, circular dichroism, and other biophysical approaches to demonstrate and characterize the binding of Zα to mRNA and rRNA fragments. Our results reveal a broad range of RNA sequences that bind to Zα and adopt Z-RNA conformations. Binding is accompanied by destabilization of neighboring A-form regions which is similar in character to what has been observed for B-Z-DNA junctions. The binding of Zα to non-CpG sequences is specific, cooperative and occurs with an affinity in the low micromolar range. This work allows us to propose a model for how Zα could influence the RNA binding specificity of ADAR1.


Asunto(s)
Adenosina Desaminasa/metabolismo , Elementos Alu/genética , Dominios Proteicos , ARN Ribosómico/metabolismo , Proteínas de Unión al ARN/metabolismo , Adenosina Desaminasa/genética , Adenosina Desaminasa/aislamiento & purificación , Adenosina Desaminasa/ultraestructura , Dicroismo Circular , Inmunidad Innata , Resonancia Magnética Nuclear Biomolecular , Conformación de Ácido Nucleico , Motivo de Reconocimiento de ARN , ARN Ribosómico/genética , ARN Ribosómico/inmunología , ARN Ribosómico/ultraestructura , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/aislamiento & purificación , Proteínas de Unión al ARN/ultraestructura , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestructura
11.
Compr Physiol ; 11(1): 1575-1589, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33577121

RESUMEN

Uncontrolled immune system activation amplifies end-organ injury in hypertension. Nonetheless, the exact mechanisms initiating this exacerbated inflammatory response, thereby contributing to further increases in blood pressure (BP), are still being revealed. While participation of lymphoid-derived immune cells has been well described in the hypertension literature, the mechanisms by which myeloid-derived innate immune cells contribute to T cell activation, and subsequent BP elevation, remains an active area of investigation. In this article, we critically analyze the literature to understand how monocytes, macrophages, dendritic cells, and polymorphonuclear leukocytes, including mast cells, eosinophils, basophils, and neutrophils, contribute to hypertension and hypertension-associated end-organ injury. The most abundant leukocytes, neutrophils, are indisputably increased in hypertension. However, it is unknown how (and why) they switch from critical first responders of the innate immune system, and homeostatic regulators of BP, to tissue-damaging, pro-hypertensive mediators. We propose that myeloperoxidase-derived pro-oxidants, neutrophil elastase, neutrophil extracellular traps (NETs), and interactions with other innate and adaptive immune cells are novel mechanisms that could contribute to the inflammatory cascade in hypertension. We further posit that the gut microbiota serves as a set point for neutropoiesis and their function. Finally, given that hypertension appears to be a key risk factor for morbidity and mortality in COVID-19 patients, we put forth evidence that neutrophils and NETs cause cardiovascular injury post-coronavirus infection, and thus may be proposed as an intriguing therapeutic target for high-risk individuals. © 2021 American Physiological Society. Compr Physiol 11:1575-1589, 2021.


Asunto(s)
Trampas Extracelulares/inmunología , Hipertensión/inmunología , Inmunidad Innata/inmunología , Neutrófilos/inmunología , Animales , /inmunología , Microbioma Gastrointestinal/inmunología , Humanos , Hipertensión/fisiopatología , Inflamación/inmunología , Inflamación/fisiopatología , Estrés Oxidativo/inmunología , /inmunología
12.
J Clin Invest ; 131(3)2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33529167

RESUMEN

BACKGROUNDDespite a rapidly growing body of literature on coronavirus disease 2019 (COVID-19), our understanding of the immune correlates of disease severity, course, and outcome remains poor.METHODSUsing mass cytometry, we assessed the immune landscape in longitudinal whole-blood specimens from 59 patients presenting with acute COVID-19 and classified based on maximal disease severity. Hospitalized patients negative for SARS-CoV-2 were used as controls.RESULTSWe found that the immune landscape in COVID-19 formed 3 dominant clusters, which correlated with disease severity. Longitudinal analysis identified a pattern of productive innate and adaptive immune responses in individuals who had a moderate disease course, whereas those with severe disease had features suggestive of a protracted and dysregulated immune response. Further, we identified coordinate immune alterations accompanying clinical improvement and decline that were also seen in patients who received IL-6 pathway blockade.CONCLUSIONThe hospitalized COVID-19 negative cohort allowed us to identify immune alterations that were shared between severe COVID-19 and other critically ill patients. Collectively, our findings indicate that selection of immune interventions should be based in part on disease presentation and early disease trajectory due to the profound differences in the immune response in those with mild to moderate disease and those with the most severe disease.FUNDINGBenaroya Family Foundation, the Leonard and Norma Klorfine Foundation, Glenn and Mary Lynn Mounger, and the National Institutes of Health.


Asunto(s)
Inmunidad Adaptativa , Inmunidad Innata , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad
13.
Sci Adv ; 7(6)2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33536217

RESUMEN

Dysregulations in the inflammatory response of the body to pathogens could progress toward a hyperinflammatory condition amplified by positive feedback loops and associated with increased severity and mortality. Hence, there is a need for identifying therapeutic targets to modulate this pathological immune response. Here, we propose a single cell-based computational methodology for predicting proteins to modulate the dysregulated inflammatory response based on the reconstruction and analysis of functional cell-cell communication networks of physiological and pathological conditions. We validated the proposed method in 12 human disease datasets and performed an in-depth study of patients with mild and severe symptomatology of the coronavirus disease 2019 for predicting novel therapeutic targets. As a result, we identified the extracellular matrix protein versican and Toll-like receptor 2 as potential targets for modulating the inflammatory response. In summary, the proposed method can be of great utility in systematically identifying therapeutic targets for modulating pathological immune responses.


Asunto(s)
/patología , Factores Inmunológicos/metabolismo , Inflamación/patología , Biología de Sistemas/métodos , /inmunología , Comunicación Celular , Citocinas/genética , Citocinas/metabolismo , Humanos , Inmunidad Innata , Linfocitos/citología , Linfocitos/inmunología , Linfocitos/metabolismo , Receptores de Quimiocina/genética , Receptores de Quimiocina/metabolismo , Índice de Severidad de la Enfermedad , Receptor Toll-Like 2/antagonistas & inhibidores , Receptor Toll-Like 2/metabolismo , Versicanos/antagonistas & inhibidores , Versicanos/metabolismo
14.
Adv Exp Med Biol ; 1275: 133-149, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33539014

RESUMEN

Immune response relies upon several intracellular signaling events. Among the protein kinases involved in these pathways, members of the protein kinase C (PKC) family are prominent molecules because they have the capacity to acutely and reversibly modulate effector protein functions, controlling both spatial distribution and dynamic properties of the signals. Different PKC isoforms are involved in distinct signaling pathways, with selective functions in a cell-specific manner.In innate system, Toll-like receptor signaling is the main molecular event triggering effector functions. Various isoforms of PKC can be common to different TLRs, while some of them are specific for a certain type of TLR. Protein kinases involvement in innate immune cells are presented within the chapter emphasizing their coordination in many aspects of immune cell function and, as important players in immune regulation.In adaptive immunity T-cell receptor and B-cell receptor signaling are the main intracellular pathways involved in seminal immune specific cellular events. Activation through TCR and BCR can have common intracellular pathways while others can be specific for the type of receptor involved or for the specific function triggered. Various PKC isoforms involvement in TCR and BCR Intracellular signaling will be presented as positive and negative regulators of the immune response events triggered in adaptive immunity.


Asunto(s)
Proteínas Quinasas , Transducción de Señal , Proteínas Portadoras , Inmunidad Innata , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores Toll-Like
15.
J Allergy Clin Immunol Pract ; 9(2): 641-650, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33551039

RESUMEN

Maturation of the adaptive immune response is typically thought to improve outcome to virus infections. However, long-standing observations of natural infections with old viruses such as Epstein-Barr virus and newer observations of emerging viruses such as severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 suggest that immune immaturity may be beneficial for outcome. Mechanistic studies and studies of patients with inborn errors of immunity have revealed that immune dysregulation reflecting inappropriate antibody and T-cell responses plays a crucial role in causing bystander inflammation and more severe disease. Further evidence supports a role for innate immunity in normally regulating adaptive immune responses. Thus, changes in immune responses that normally occur with age may help explain an apparent protective role of immune immaturity during virus infections.


Asunto(s)
Envejecimiento/inmunología , Virosis/inmunología , Inmunidad Adaptativa , Animales , Humanos , Inmunidad Innata
16.
Biomed Res Int ; 2021: 8870425, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33564683

RESUMEN

Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus Disease 2019 (COVID-19) infections are the three epidemiological diseases caused by the Coronaviridae family. Perceiving the immune responses in these infections and the escape of viruses could help us design drugs and vaccines for confronting these infections. This review investigates the innate and adaptive immune responses reported in the infections of the three coronaviruses SARS, MERS, and COVID-19. Moreover, the present study can trigger researchers to design and develop new vaccines and drugs based on immune system responses. In conclusion, due to the need for an effective and efficient immune stimulation against coronavirus, a combination of several strategies seems necessary for developing the vaccine.


Asunto(s)
/inmunología , Infecciones por Coronavirus/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Virus del SRAS/inmunología , Síndrome Respiratorio Agudo Grave/inmunología , Inmunidad Adaptativa , Animales , Infecciones por Coronavirus/prevención & control , Humanos , Inmunidad Innata , Síndrome Respiratorio Agudo Grave/prevención & control
17.
Int J Mol Sci ; 22(3)2021 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-33498725

RESUMEN

Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.


Asunto(s)
/inmunología , Células Dendríticas/inmunología , /inmunología , Inmunidad Adaptativa , Animales , /terapia , Células Dendríticas/patología , Humanos , Inmunidad Innata , Linfocitos T/inmunología
18.
J Insect Sci ; 21(1)2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33511414

RESUMEN

Insect innate immunity is initiated by the special recognition and binding of the foreign pathogens, which is accomplished by the pattern recognition receptors (PRRs). As an important type of PRRs, C-type lectins (CTLs) play various roles in insect innate immunity, including pathogen recognition, stimulation of prophenoloxidase, regulation of cellular immunity and so on. In this study, we have cloned the full-length cDNA of a CTL gene named CTL-S6 from the silkworm, Bombyx mori. The open reading frame (ORF) of B. mori CTL-S6 encodes 378 amino acids, which contain a secretion signal peptide. The mRNA of CTL-S6 exhibited the highest transcriptional level in the midgut. Its transcriptional level increased dramatically in fat body and hemocytes upon Escherichia coli or Micrococcus luteus challenge. Purified recombinant CTL-S6 could bind to bacterial cell wall components, including peptidoglycan (PGN, from Bacillus subtilis) and lipopolysaccharide (LPS, from E. coli 0111:B4), and recombinant CTL-S6 was involved in the encapsulation and melanization of hemocytes. Furthermore, the addition of recombinant CTL-S6 to the hemolymph of silkworm resulted in a significant increase in phenoloxidase activity. Overall, our results indicated that B. mori CTL-S6 may serve as a PRR for the recognition of foreign pathogens, prophenoloxidase pathway stimulation and involvement in the innate immunity.


Asunto(s)
Escherichia coli/fisiología , Inmunidad Innata/genética , Proteínas de Insectos/genética , Lectinas Tipo C/genética , Micrococcus luteus/fisiología , Receptores de Reconocimiento de Patrones/genética , Transcripción Genética , Secuencia de Aminoácidos , Animales , Bombyx , Cuerpo Adiposo/inmunología , Perfilación de la Expresión Génica , Hemocitos/inmunología , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Lectinas Tipo C/química , Lectinas Tipo C/metabolismo , Filogenia , Receptores de Reconocimiento de Patrones/química , Receptores de Reconocimiento de Patrones/metabolismo , Alineación de Secuencia
19.
Mediators Inflamm ; 2021: 8874339, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33505220

RESUMEN

Causes of mortality from COVID-19 include respiratory failure, heart failure, and sepsis/multiorgan failure. TLR4 is an innate immune receptor on the cell surface that recognizes pathogen-associated molecular patterns (PAMPs) including viral proteins and triggers the production of type I interferons and proinflammatory cytokines to combat infection. It is expressed on both immune cells and tissue-resident cells. ACE2, the reported entry receptor for SARS-CoV-2, is only present on ~1-2% of the cells in the lungs or has a low pulmonary expression, and recently, the spike protein has been proposed to have the strongest protein-protein interaction with TLR4. Here, we review and connect evidence for SARS-CoV-1 and SARS-CoV-2 having direct and indirect binding to TLR4, together with other viral precedents, which when combined shed light on the COVID-19 pathophysiological puzzle. We propose a model in which the SARS-CoV-2 spike glycoprotein binds TLR4 and activates TLR4 signalling to increase cell surface expression of ACE2 facilitating entry. SARS-CoV-2 also destroys the type II alveolar cells that secrete pulmonary surfactants, which normally decrease the air/tissue surface tension and block TLR4 in the lungs thus promoting ARDS and inflammation. Furthermore, SARS-CoV-2-induced myocarditis and multiple-organ injury may be due to TLR4 activation, aberrant TLR4 signalling, and hyperinflammation in COVID-19 patients. Therefore, TLR4 contributes significantly to the pathogenesis of SARS-CoV-2, and its overactivation causes a prolonged or excessive innate immune response. TLR4 appears to be a promising therapeutic target in COVID-19, and since TLR4 antagonists have been previously trialled in sepsis and in other antiviral contexts, we propose the clinical trial testing of TLR4 antagonists in the treatment of severe COVID-19. Also, ongoing clinical trials of pulmonary surfactants in COVID-19 hold promise since they also block TLR4.


Asunto(s)
/metabolismo , Regulación de la Expresión Génica , Virus del SRAS , Receptor Toll-Like 4/metabolismo , Antivirales/uso terapéutico , Proliferación Celular , Humanos , Inmunidad Innata , Inflamación , Interferón Tipo I/metabolismo , Pulmón/metabolismo , Miocardio/metabolismo , Unión Proteica , Transducción de Señal , Glicoproteína de la Espiga del Coronavirus/metabolismo , Tensoactivos
20.
Vet Res ; 52(1): 14, 2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509253

RESUMEN

Infectious bronchitis virus (IBV) is a pathogenic coronavirus with high morbidity and mortality in chicken breeding. Macrophages with normal biofunctions are essential for host immune responses. In this study, the HD11 chicken macrophage cell line and chicken peripheral blood mononuclear cell-derived macrophages (PBMCs-Mφ) were infected with IBV at multiplicity of infection (MOI) of 10. The dynamic changes of their biofunctions, including cell viability, pathogen elimination function, phagocytic ability, and gene expressions of related proteins/mediators in innate and acquired immunity, inflammation, autophagy and apoptosis were analyzed. Results showed that IBV infection decreased chicken macrophage viability and phagocytic ability, and increased pathogen elimination function. Moreover, IBV augmented the gene expressions of most related proteins in macrophages involved in multiple host bioprocesses, and the dynamic changes of gene expressions had a close relationship with virus replication. Among them, MHCII, Fc receptor, TLR3, IFN-α, CCL4, MIF, IL-1ß, IL-6, and iNOS showed significantly higher expressions in IBV-infected cells. However, TLR7, MyD88, MDA5, IFN-γ, MHCII, Fc receptor, MARCO, CD36, MIF, XCL1, CXCL12, TNF-α, iNOS, and IL-10 showed early decreased expressions. Overall, chicken macrophages play an important role in host innate and acquired immune responses to resist IBV infection, despite early damage or suppression. Moreover, the IBV-induced autophagy and apoptosis might participate in the virus-host cell interaction which is attributed to the biological process.


Asunto(s)
Regulación Viral de la Expresión Génica/fisiología , Virus de la Bronquitis Infecciosa/fisiología , Leucocitos Mononucleares/virología , Macrófagos/virología , Inmunidad Adaptativa , Animales , Apoptosis , Autofagia , Línea Celular , Supervivencia Celular , Quimiocinas/genética , Quimiocinas/metabolismo , Pollos , Efecto Citopatogénico Viral , ADN Complementario/genética , Citometría de Flujo/veterinaria , Inmunidad Innata , Inflamación , Interferones/metabolismo , Leucocitos Mononucleares/fisiología , Macrófagos/fisiología , Óxido Nítrico/análisis , Fagocitosis , ARN Viral/genética , ARN Viral/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Organismos Libres de Patógenos Específicos
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