共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Katja Pirc Vesna Hodnik Tina Snoj Tea Lenar
i
Simon Caserman Marjetka Podobnik Hannah Bhm Isabell Albert Anita Kotar Janez Plavec Jure Boriek Martina Damuzzo Alessandra Magistrato Boris Brus Izidor Sosi
Stanislav Gobec Thorsten Nürnberger Gregor Anderluh 《PLoS pathogens》2021,17(4)
The lack of efficient methods to control the major diseases of crops most important to agriculture leads to huge economic losses and seriously threatens global food security. Many of the most important microbial plant pathogens, including bacteria, fungi, and oomycetes, secrete necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs), which critically contribute to the virulence and spread of the disease. NLPs are cytotoxic to eudicot plants, as they disturb the plant plasma membrane by binding to specific plant membrane sphingolipid receptors. Their pivotal role in plant infection and broad taxonomic distribution makes NLPs a promising target for the development of novel phytopharmaceutical compounds. To identify compounds that bind to NLPs from the oomycetes Pythium aphanidermatum and Phytophthora parasitica, a library of 587 small molecules, most of which are commercially unavailable, was screened by surface plasmon resonance. Importantly, compounds that exhibited the highest affinity to NLPs were also found to inhibit NLP-mediated necrosis in tobacco leaves and Phytophthora infestans growth on potato leaves. Saturation transfer difference-nuclear magnetic resonance and molecular modelling of the most promising compound, anthranilic acid derivative, confirmed stable binding to the NLP protein, which resulted in decreased necrotic activity and reduced ion leakage from tobacco leaves. We, therefore, confirmed that NLPs are an appealing target for the development of novel phytopharmaceutical agents and strategies, which aim to directly interfere with the function of these major microbial virulence factors. The compounds identified in this study represent lead structures for further optimization and antimicrobial product development. 相似文献
3.
4.
To cause disease, bacterial pathogens must first breach physical barriers, such as the mucous membrane that lines organs, and then successfully replicate and disseminate while avoiding destruction by the immune system. Many bacterial pathogens accomplish this by secreting proteins into their host environment, which act to subvert or dampen the expanding immune response. Here, we discuss how bacterial pathogens use an arsenal of secreted virulence proteins to modify the outcome of innate immune activation by altering how the immune system recognizes microbial invaders. 相似文献
5.
Treponemal phospholipids inhibit innate immune responses induced by pathogen-associated molecular patterns 总被引:3,自引:0,他引:3
Host innate immune responses to microbial components, known as pathogen-associated molecular patterns (PAMPs), are regulated and modified by cellular receptors and serum proteins, including Toll-like receptors (TLRs), CD14, and LPS-binding protein (LBP). We demonstrated that a treponemal membrane lipid inhibited PAMPs-induced immune responses. The chemical structure of the lipid was elucidated as a phosphatidylglycerol (PG) derivative, which is scarce in most mammalian tissues, but relatively abundant in treponemal membrane lipids. Natural and synthetic PG counterparts as well as related natural anionic phospholipids, phosphatidylinositol, phosphatidylserine, and cardiolipin, also demonstrated an inhibitory effect. Further, we noted that PG inhibited PAMPs-induced immune responses by blocking the binding of PAMPs with LBP and CD14. In addition, PG decreased proinflammatory cytokine production in serum of LPS-injected mice and depressed abscess formation in mice infected with treponemes. These results suggest that treponemal phospholipid interfere the function of LBP/CD14 and act as a modulator of innate immune responses. 相似文献
6.
7.
Nep1-like proteins from plant pathogens: recruitment and diversification of the NPP1 domain across taxa 总被引:1,自引:0,他引:1
An emerging group of proteins found in many plant pathogens are related to their ability to cause plant cell death. These proteins may be identified by the presence of a common NPP1 (necrosis-inducing Phytophthora protein) domain, and have collectively been named NLPs (Nep1-like proteins). The NLPs are distinguished by their wide distribution across taxa and their broad spectrum of activity against dicotyledonous plants. The function of NLPs is not known but there is strong evidence that they may act as positive virulence factors, accelerating disease and pathogen growth in plant hosts. Interest in NLPs is gaining momentum as more members of this protein family are discovered in more species of plant pathogens. 相似文献
8.
Beutler B Hoebe K Georgel P Tabeta K Du X 《Microbes and infection / Institut Pasteur》2004,6(15):1374-1381
The innate immune system senses pathogens largely through signals initiated by a collection of phylogenetically related proteins known as "Toll-like receptors" (TLRs), of which 10 representatives are encoded in the human genome. Our understanding of the sensing role played by the TLRs began with the positional cloning of a spontaneous mutation (Lps(d)) in the gene encoding the mammalian lipopolysaccharide (LPS) receptor. Other key innate immunity proteins have been disclosed by germline mutagenesis, and are discussed in the present review. 相似文献
9.
Heat shock proteins: the fountainhead of innate and adaptive immune responses 总被引:9,自引:0,他引:9
下载免费PDF全文
![点击此处可从《Cell stress & chaperones》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The ability of heat shock proteins to (1) chaperone peptides, including antigenic peptides; (2) interact with antigen-presenting cells through a receptor; (3) stimulate antigen-presenting cells to secrete inflammatory cytokines; and (4) mediate maturation of dendritic cells, makes them a unique starting point for generation of immune responses. These properties also permit the use of heat shock proteins for development of a new generation of prophylactic and therapeutic vaccines against cancers and infectious diseases. 相似文献
10.
Juckem LK Boehme KW Feire AL Compton T 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(7):4965-4977
Infection of permissive fibroblasts with human CMV (HCMV, AD169) is accompanied by a robust activation of innate immune defense. In this study, we show that inflammatory cytokine (IC) secretion and activation of the type I IFN pathway (alphabeta IFN) are initiated through distinct mechanisms. HCMV is recognized by TLR2 leading to the NF-kappaB activation and IC secretion. However, the IFN response to HCMV is not a TLR2-dependent process, as a dominant negative TLR2 does not affect the antiviral response to infection. Additionally, bafilomycin, an endosomal acidification inhibitor, has no effect on HCMV-induced IFN responses suggesting that IFN signaling is independent of endosomal resident TLRs. By contrast, disruption of lipid rafts by depletion of cellular cholesterol inhibits both HCMV entry as well as IFN responses. Cholesterol depletion had no effect on the induction of ICs by HCMV, illustrating a biological distinction at the cellular level with the initiation of innate immune pathways. Furthermore, HCMV entry inhibitors block IFN responses but not IC signaling. In particular, blocking the interaction of HCMV with beta(1) integrin diminished IFN signaling, suggesting that this virus-cell interaction or subsequent downstream steps in the entry pathway are critical for downstream signal transduction events. These data show that HCMV entry and IFN signaling are coordinated processes that require cholesterol-rich microdomains, whereas IC signaling is activated through outright sensing via TLR2. These findings further highlight the complexity and sophistication of innate immune responses at the earliest points in HCMV infection. 相似文献
11.
The innate immune system has a key role in the mammalian immune response. Recent research has demonstrated that mitochondria participate in a broad range of innate immune pathways, functioning as signalling platforms and contributing to effector responses. In addition to regulating antiviral signalling, mounting evidence suggests that mitochondria facilitate antibacterial immunity by generating reactive oxygen species and contribute to innate immune activation following cellular damage and stress. Therefore, in addition to their well-appreciated roles in cellular metabolism and programmed cell death, mitochondria appear to function as centrally positioned hubs in the innate immune system. Here, we review the emerging knowledge about the roles of mitochondria in innate immunity. 相似文献
12.
13.
Luo ZQ 《Cellular microbiology》2012,14(1):19-27
Legionella pneumophila is a facultative intracellular pathogen capable of replicating in a wide spectrum of cells. Successful infection by Legionella requires the Dot/Icm type IV secretion system, which translocates a large number of effector proteins into infected cells. By co-opting numerous host cellular processes, these proteins function to establish a specialized organelle that allows bacterial survival and proliferation. Even within the vacuole, L. pneumophila triggers robust immune responses. Recent studies reveal that a subset of Legionella effectors directly target some basic components of the host innate immunity systems such as phagosome maturation. Others play essential roles in engaging the host innate immune surveillance system. This review will highlight recent progress in our understanding of these interactions and discuss implications for the study of the immune detection mechanisms. 相似文献
14.
Nep1-like proteins (NLPs), produced by an array of unrelated microorganisms, are phytotoxic for dicotyledonous plant cells but their mode of action has not yet been established. Two paralogous NLPs from the necrotrophic plant pathogenic fungus Botrytis cinerea were characterized, designated BcNEP1 and BcNEP2. Both proteins were produced in the heterologous host Pichia pastoris and purified to homogeneity. The localization of fluorescently labelled proteins was studied and mechanisms of cell death were investigated in protoplasts and suspension cells. Purified BcNEP1 and BcNEP2 caused necrosis in all dicotyledonous plant species tested, but not in monocotyledons. A synthetic heptapeptide comprising a sequence (GHRHDWE) that is conserved in all NLPs did not cause symptoms and was unable to interfere with necrosis induction by BcNEP1 and BcNEP2 proteins. Fluorescently labelled BcNEP1 and BcNEP2 proteins were associated with plasma membranes and the nuclear envelope, as well as in the nucleolus of responding plant cells. A strong hydrogen peroxide (H(2)O(2)) accumulation was observed in chloroplasts. The death process was characterized by TUNEL assays as apoptosis, necrosis or intermediate forms of both. BcNEP1- and BcNEP2-induced cell death execution could not be abolished by specific inhibitors. These results provide further information on mechanisms of NLP-inflicted cell death. 相似文献
15.
The activation of innate immune responses by nucleic acids is critical to host responses against pathogens, such as viruses; however, nucleic acids can also trigger the development and/or exacerbation of pathogenic responses such as autoimmunity. We previously demonstrated that the selective activation of nucleic acid-sensing cytosolic and Toll-like receptors is contingent on the promiscuous sensing of nucleic acids by high-mobility group box proteins (HMGBs). Basides these findings, we also found that nonimmunogenic nucleotide with high-affinity HMGB binding, termed ISM ODN, functions as suppressing agent for nucleic acid-activated innate immune responses. In this review, we aim to summerize this novel feature of HMGB proteins in nucleic acid-mediated innate immune responses. In addition, we will discuss the inhibitory effect of nonimmunogenic oligodeoxynucleotides (ni-ODNs) targeting HMGB proteins. 相似文献
16.
Crohn's disease (CD) is a chronic intestinal inflammatory pathology, which develops as a result of innate immune signals, such as the activation of Toll-like receptors (TLRs), and adaptive immune signals, including Th1 cytokine release. We have recently demonstrated in TNBS-induced colitis, a murine model of CD, that VIP plays a homeostatic role, by reducing TNBS-induced TLR2 and TLR4 expression to control levels. The purpose of this paper is to elucidate for the first time, the physiological relevance of VIP specific control of innate and adaptive immune responses through TLR2 and TLR4 ligands. In addition, we investigated the effect of VIP on regulatory activity of T regulatory (Treg) cells in the TNBS-colitis model. First, we found that VIP downregulated the inflammatory response elicited in mesenteric lymph node cell cultures by treatment with the TLR2 ligand Pam3Cys, or the TLR4 ligand lipopolysaccharide (LPS), reducing the production of the chemokine CXCL1. Also, treatment with VIP impaired the induction of Th1 responses by decreasing p70 interleukin (IL)-12 and interferon gamma (IFN-γ) levels after TLR2/TLR4 stimulation in culture. Besides, VIP treatment restored in vivo the numbers of TLR2 and TLR4 positive CD4+CD25+ T lymphocytes, augmented by TNBS administration, and increased the expression of molecules involved in regulatory T cell function, such as Foxp3 and TGF-β. In conclusion, the ability of VIP to down-regulate uncontrolled inflammation by targeting TLR-mediated responses and regulatory T cell activity could be used as a new alternative therapy for intestinal inflammatory/autoimmune disorders. 相似文献
17.
RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs 总被引:1,自引:0,他引:1
Park JH Kim YG McDonald C Kanneganti TD Hasegawa M Body-Malapel M Inohara N Núñez G 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(4):2380-2386
RICK is a kinase that has been implicated in Nod1 and Nod2 signaling. In addition, RICK has been proposed to mediate TLR signaling in that its absence confers reduced responses to certain bacterial products such as LPS. We show here that macrophages and mice lacking RICK are defective in their responses to Nod1 and Nod2 agonists but exhibit unimpaired responses to synthetic and highly purified TLR agonists. Furthermore, production of chemokines induced by the bacterial dipeptide gamma-d-glutamyl-meso-diaminopimelic acid was intact in MyD88 deficient mice but abolished in RICK-null mice. Stimulation of macrophages with muramyl dipeptide, the Nod2 activator, enhanced immune responses induced by LPS, IFN-gamma, and heat-killed Listeria in wild-type but not in RICK- or Nod2-deficient macrophages. Finally, we show that the absence of RICK or double deficiency of Nod1 and Nod2 was associated with reduced cytokine production in Listeria-infected macrophages. These results demonstrate that RICK functions in innate immunity by mediating Nod1 and Nod2 signaling but not TLR-mediated immune responses. 相似文献
18.
Host organisms have developed sophisticated antiviral responses in order to defeat emerging influenza A viruses (IAVs). At the same time IAVs have evolved immune evasion strategies. The immune system of mammals provides several lines of defence to neutralize invading pathogens or limit their replication. Here, we summarize the mammalian innate and adaptive immune mechanisms involved in host defence against viral infection and review strategies by which IAVs avoid, circumvent or subvert these mechanisms. We highlight well‐characterized, as well as recently described features of this intriguing virus‐host molecular battle. 相似文献
19.
It has long been known that malaria infection causes host immune modulation by various mechanisms. However, the role of Toll-like receptors (TLRs) in mediating innate immune responses to parasite-derived components during the blood stages of malaria has only recently been described. TLRs might have an important role in pathogenesis during malaria infection, as supported by genetic analyses in mice and humans. Moreover, recent findings revealed that sporozoites can partially differentiate in lymph nodes and that liver stages induce the formation of previously unknown parasite-filled vesicles (merosomes) that could function as immune escape machinery. Elucidation of the mechanisms by which the host innate immune system responds to, and/or is manipulated by, Plasmodium infection will hopefully lead to discoveries of potential targets that will ultimately prevent and/or intervene in malaria infection. 相似文献
20.
The inflammasome is a large multiprotein complex whose assembly leads to the activation of caspase-1, which promotes the maturation of proinflammatory cytokines interleukin-1beta (IL-1beta) and IL-18. Proteins encoded by the nucleotide-binding domain and leucine-rich repeat (NLR) containing gene family form the central components of inflammasomes and act as intracellular sensors to detect cytosolic microbial components and "danger" signals (such as ATP and toxins). The inflammasome not only plays a pivotal role in innate immune responses toward pathogens but also mediates the activity of aluminum adjuvants. Thus, the inflammasome and associated signaling pathways are attractive targets for new therapeutics and vaccines. 相似文献