共查询到20条相似文献,搜索用时 406 毫秒
1.
Nicola Raftery Nigel J. Stevenson 《Cellular and molecular life sciences : CMLS》2017,74(14):2525-2535
Interferon-alpha (IFN-α) is a potent anti-viral cytokine, critical to the host immune response against viruses. IFN-α is first produced upon viral detection by pathogen recognition receptors. Following its expression, IFN-α embarks upon a complex downstream signalling cascade called the JAK/STAT pathway. This signalling pathway results in the expression of hundreds of effector genes known as interferon stimulated genes (ISGs). These genes are the basis for an elaborate effector mechanism and ultimately, the clearance of viral infection. ISGs mark an elegant mechanism of anti-viral host defence that warrants renewed research focus in our global efforts to treat existing and emerging viruses. By understanding the mechanistic role of individual ISGs we anticipate the discovery of a new “treasure trove” of anti-viral mediators that may pave the way for more effective, targeted and less toxic anti-viral therapies. Therefore, with the aim of highlighting the value of the innate type 1 IFN response in our battle against viral infection, this review outlines both historic and recent advances in understanding the IFN-α JAK/STAT pathway, with a focus on new research discoveries relating to specific ISGs and their potential role in curing existing and future emergent viral infections. 相似文献
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Nollaig M. Bourke Silvia Napoletano Ciaran Bannan Suaad Ahmed Colm Bergin Áine McKnight Nigel J. Stevenson 《Cellular and molecular life sciences : CMLS》2018,75(5):775-783
Viral infections, including HIV, trigger the production of type I interferons (IFNs), which in turn, activate a signalling cascade that ultimately culminates with the expression of anti-viral proteins. Mounting evidence suggests that type I IFNs, in particular IFN-α, play a pivotal role in limiting acute HIV infection. Highly active anti-retroviral treatment reduces viral load and increases life expectancy in HIV positive patients; however, it fails to fully eliminate latent HIV reservoirs. To revisit HIV as a curable disease, this article reviews a body of literature that highlights type I IFNs as mediators in the control of HIV infection, with particular focus on the anti-HIV restriction factors induced and/or activated by IFN-α. In addition, we discuss the relevance of type I IFN treatment in the context of HIV latency reversal, novel therapeutic intervention strategies and the potential for full HIV clearance. 相似文献
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The innate immunity of the central nervous system in chronic pain: The role of Toll-like receptors 总被引:1,自引:0,他引:1
Toll-like receptors (TLRs) are a family of pattern recognition receptors that mediate innate immune responses to stimuli from
pathogens or endogenous signals. Under various pathological conditions, the central nervous system (CNS) mounts a well-organized
innate immune response, in which glial cells, in particular microglia, are activated. Further, the innate immune system has
emerged as a promising target for therapeutic control of development and persistence of chronic pain. Especially, microglial
cells respond to peripheral and central infection, injury, and other stressor signals arriving at the CNS and initiate a CNS
immune activation that might contribute to chronic pain facilitation. In the orchestration of this limited immune reaction,
TLRs on microglia appear to be most relevant in triggering and tailoring microglial activation, which might be a driving force
of chronic pain. New therapeutic approaches targeting the CNS innate immune system may achieve the essential pharmacological
control of chronic pain.
Received 21 November 2006; received after revision 8 January 2007; accepted 7 February 2007 相似文献
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The STING pathway and regulation of innate immune signaling in response to DNA pathogens 总被引:1,自引:1,他引:0
The innate immune system has evolved a variety of sensing mechanisms to detect and counter microbial invasion. These include
the Toll-like receptor (TLR), cytoplasmic, nucleotide binding oligomerization domain (NOD)-like receptor and RIG-I-like helicase
(RLH) pathways. However, how the cell detects pathogen-associated DNA to trigger host defense, including the production of
interferon, remains to be fully clarified. Understanding these processes could have profound implications into how we understand
and treat a variety of microbial-related disease, including viral-associated cancers, as well as autoimmune disorders. Recently,
an endoplasmic reticulum-associated molecule referred to as STING (for stimulator of interferon genes) was isolated and shown
to be critical for regulating the production of IFN in response to cytoplasmic DNA. Here, we review recent discoveries relating
to the detection of foreign DNA, including the importance of the STING and inflammasome pathways and the triggering of innate
signaling processes. 相似文献
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Stefan F. Martin 《Cellular and molecular life sciences : CMLS》2014,71(21):4115-4130
The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This “design feature” of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed. 相似文献
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Lamine Alaoui Gustavo Palomino Sandy Zurawski Gerard Zurawski Sixtine Coindre Nathalie Dereuddre-Bosquet Camille Lecuroux Cecile Goujard Bruno Vaslin Christine Bourgeois Pierre Roques Roger Le Grand Olivier Lambotte Benoit Favier 《Cellular and molecular life sciences : CMLS》2018,75(10):1871-1887
Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response. 相似文献
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Identification of the bioactive peptide PEC-60 in brain 总被引:1,自引:0,他引:1
Norberg A Gruber S Angelucci F Renlund S Wadensten H Efendic S Ostenson CG Jörnvall H Sillard R Mathé AA 《Cellular and molecular life sciences : CMLS》2003,60(2):378-381
PEC-60 is a 60-residue peptide originally isolated from pig intestine. It inhibits glucose-induced insulin secretion from
perfused pancreas in a hormonal manner and also has biological activity in the immune system. PEC-60-like immunoreactive material
has been reported in catecholamine neurons of the central and peripheral nervous systems, but the peptide has not been identified
from that material. We have now isolated PEC-60 from pig and rat brains with a method that combines column purification procedures
with the specificity of a radioimmunoassay and the sensitivity of mass spectrometry to directly identify the peptide. The
results show that PEC-60, like many other peptides, is expressed in the gastrointestinal tract and the central nervous system.
The specific regional brain distribution and interaction with classical neurotransmitters raise the possibility that PEC-60may
play a role in the central nervous system disorders involving dopamine dysregulation.
Received 6 December 2002; received after revision 10 December 2002; accepted 11 December 2002
RID="*"
ID="*"Corresponding author. 相似文献
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Darío Acuña-Castroviejo Ibtissem Rahim Carlos Acuña-Fernández Marisol Fernández-Ortiz Jorge Solera-Marín Ramy K. A. Sayed María E. Díaz-Casado Iryna Rusanova Luis C. López Germaine Escames 《Cellular and molecular life sciences : CMLS》2017,74(21):3965-3987
After the characterization of the central pacemaker in the suprachiasmatic nucleus, the expression of clock genes was identified in several peripheral tissues including the immune system. The hierarchical control from the central clock to peripheral clocks extends to other functions including endocrine, metabolic, immune, and mitochondrial responses. Increasing evidence links the disruption of the clock genes expression with multiple diseases and aging. Chronodisruption is associated with alterations of the immune system, immunosenescence, impairment of energy metabolism, and reduction of pineal and extrapineal melatonin production. Regarding sepsis, a condition coursing with an exaggerated response of innate immunity, experimental and clinical data showed an alteration of circadian rhythms that reflects the loss of the normal oscillation of the clock. Moreover, recent data point to that some mediators of the immune system affects the normal function of the clock. Under specific conditions, this control disappears reactivating the immune response. So, it seems that clock gene disruption favors the innate immune response, which in turn induces the expression of proinflammatory mediators, causing a further alteration of the clock. Here, the clock control of the mitochondrial function turns off, leading to a bioenergetic decay and formation of reactive oxygen species that, in turn, activate the inflammasome. This arm of the innate immunity is responsible for the huge increase of interleukin-1β and entrance into a vicious cycle that could lead to the death of the patient. The broken clock is recovered by melatonin administration, that is accompanied by the normalization of the innate immunity and mitochondrial homeostasis. Thus, this review emphasizes the connection between clock genes, innate immunity and mitochondria in health and sepsis, and the role of melatonin to maintain clock homeostasis. 相似文献
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G. D. Das 《Cellular and molecular life sciences : CMLS》1977,33(9):1179-1180
Summary Binucleated neurons were studied in the central nervous system of the rat and the rabbit. They were present in the young as well as the adult animals. The animals injected with thymidine-H3 during their embryonic development showed labelled binucleated neurons. It is suggested that the neurons become binucleated during neuroembryogenesis, and differentiate into normal neurons morphologically and physiologically.Supported by NIH Research grant No. NS-08817-05. 相似文献
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Siobhán C. Cowley 《Cellular and molecular life sciences : CMLS》2014,71(24):4831-4840
Mucosa-associated invariant T (MAIT) cells are a unique population of innate T cells that are abundant in humans. These cells possess an evolutionarily conserved invariant T cell receptor α chain restricted by the nonpolymorphic class Ib major histocompatibility (MHC) molecule, MHC class I-related protein (MR1). The recent discovery that MAIT cells are activated by MR1-bound riboflavin metabolite derivatives distinguishes MAIT cells from all other αβ T cells in the immune system. Since mammals lack the capacity to synthesize riboflavin, intermediates from the riboflavin biosynthetic pathway are distinct microbial molecular patterns that provide a unique signal to the immune system. Multiple lines of evidence suggest that MAIT cells, which produce important cytokines such as IFN-γ, TNF, and IL-17A, have the potential to influence immune responses to a broad range of pathogens. Here we will discuss our current understanding of MAIT cell biology and their role in pathogen defense. 相似文献
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Intestinal epithelial barrier and mucosal immunity 总被引:12,自引:0,他引:12
Müller CA Autenrieth IB Peschel A 《Cellular and molecular life sciences : CMLS》2005,62(12):1297-1307
The innate immune system plays a crucial role in maintaining the integrity of the intestine and protecting the host against a vast number of potential microbial pathogens from resident and transient gut microflora. Mucosal epithelial cells and Paneth cells produce a variety of antimicrobial peptides (defensins, cathelicidins, crytdinrelated sequence peptides, bactericidal/permeabilityincreasing protein, chemokine CCL20) and bacteriolytic enzymes (lysozyme, group IIA phospholipase A2) that protect mucosal surfaces and crypts containing intestinal stem cells against invading microbes. Many of the intestinal antimicrobial molecules have additional roles of attracting leukocytes, alarming the adaptive immune system or neutralizing proinflammatory bacterial molecules. Dysfunction of components of the innate immune system has recently been implicated in chronic inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, illustrating the pivotal role of innate immunity in maintaining the delicate balance between immune tolerance and immune response in the gut. 相似文献
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de Wit PJ 《Cellular and molecular life sciences : CMLS》2007,64(21):2726-2732
Plants have an innate immunity system to defend themselves against pathogens. With the primary immune system, plants recognize
microbe-associated molecular patterns (MAMPs) of potential pathogens through pattern recognition receptors (PRRs) that mediate
a basal defense response. Plant pathogens suppress this basal defense response by means of effectors that enable them to cause
disease. With the secondary immune system, plants have gained the ability to recognize effector-induced perturbations of host
targets through resistance proteins (RPs) that mediate a strong local defense response that stops pathogen growth. Both primary
and secondary immune responses in plants depend on germ line-encoded PRRs and RPs. During induction of local immune responses,
systemic immune responses also become activated, which predispose plants to become more resistant to subsequent pathogen attacks.
This review gives an update on recent findings that have enhanced our understanding of plant innate immunity and the arms
race between plants and their pathogens.
Received 24 June 2007; received after revision 18 July 2007; accepted 15 August 2007 相似文献
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Zhi-Jun Zhang Bao-Chun Jiang Yong-Jing Gao 《Cellular and molecular life sciences : CMLS》2017,74(18):3275-3291
Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron–glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain. 相似文献
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Summary The concentration of noradrenaline (NA) and of adrenaline (A) in plasma was measured before and 3, 30 and 60 min after single and repeated electroconvulsive shocks (ECS). Single ECS resulted in an activation of the sympathoadrenal medullary system; however, after the treatment had been repeated 4 times there was evidence of a diminished response of the peripheral sympathetic nervous system in comparison to the response to the first ECS. 相似文献
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Victor Tapias Xiaoping Hu Kelvin C. Luk Laurie H. Sanders Virginia M. Lee J. Timothy Greenamyre 《Cellular and molecular life sciences : CMLS》2017,74(15):2851-2874
Intracellular accumulation of α-synuclein (α-syn) are hallmarks of synucleinopathies, including Parkinson’s disease (PD). Exogenous addition of preformed α-syn fibrils (PFFs) into primary hippocampal neurons induced α-syn aggregation and accumulation. Likewise, intrastriatal inoculation of PFFs into mice and non-human primates generates Lewy bodies and Lewy neurites associated with PD-like neurodegeneration. Herein, we investigate the putative effects of synthetic human PFFs on cultured rat ventral midbrain dopamine (DA) neurons. A time- and dose-dependent accumulation of α-syn was observed following PFFs exposure that also underwent phosphorylation at serine 129. PFFs treatment decreased the expression levels of synaptic proteins, caused alterations in axonal transport-related proteins, and increased H2AX Ser139 phosphorylation. Mitochondrial impairment (including modulation of mitochondrial dynamics-associated protein content), enhanced oxidative stress, and an inflammatory response were also detected in our experimental paradigm. In attempt to unravel a potential molecular mechanism of PFFs neurotoxicity, the expression of inducible nitric oxide synthase was blocked; a significant decline in protein nitration levels and protection against PFFs-induced DA neuron death were observed. Combined exposure to PFFs and rotenone resulted in an additive toxicity. Strikingly, many of the harmful effects found were more prominent in DA rather than non-DA neurons, suggestive of higher susceptibility to degenerate. These findings provide new insights into the role of α-syn in the pathogenesis of PD and could represent a novel and valuable model to study DA-related neurodegeneration. 相似文献
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Bleakman D 《Cellular and molecular life sciences : CMLS》1999,56(7-8):558-566
Glutamate is the primary neurotransmitter in the central nervous system. One of the classes of ionotropic glutamate receptors is kainate receptors. Recent developments in the pharmacology of kainate receptors have resulted in the emergence of several selective agonists and antagonists. These compounds have allowed scientists to begin to probe the functional properties of these receptors in neurons and gain a better understanding of the role of these receptors in the nervous system. 相似文献