Recognition Of Pathogen-associated Molecular Patterns Research Articles

Transcriptome profiling reveals response genes for downy mildew resistance in cucumber.

We discovered a potential defense pathway of cucumber to downy mildew. The signaling that activates the pathways of ROS and lignin accumulation may play an important role in the defense response. Many resistance genes were identified by transcriptome analysis. Downy mildew (DM), caused by Pseudoperonospora cubensis, is one of the most destructive diseases and causes severe yield losses of cucumber. However, the genes and pathways involved in regulating DM resistance were still poorly understood. In our study, we observed that the highly sensitive inbred line 53 (IL53) exhibited more severe disease symptoms than the highly resistant inbred line 51 (IL51) under P. cubensis infection. Furthermore, lignin, limiting the germination and extension of P. cubensis, and H2O2, as a signaling molecule during the resistant process, were both shown to increase, indicating that the signaling that activates these pathways might be responsible for the resistance divergence between IL51 and IL53. Transcriptome analysis, using the resistant and susceptible pools in F2 populations with IL51 and IL53 as parents, showed that a series of differentially expressed genes was involved in multiple functions of defense response: pathogen-associated molecular pattern recognition, signal transduction, reactive oxygen species and lignin accumulation, and transcription regulators. Combining physiological data with transcriptomes, we predicted a potential molecular mechanism of cucumber resistance to DM. Our research provided a foundation for further studies on the mechanism of cucumber resistance to DM.

Host Cell Restriction Factors of Bunyaviruses and Viral Countermeasures

The Bunyavirales order comprises more than 500 viruses (generally defined as bunyaviruses) classified into 12 families. Some of these are highly pathogenic viruses infecting different hosts, including humans, mammals, reptiles, arthropods, birds, and/or plants. Host cell sensing of infection activates the innate immune system that aims at inhibiting viral replication and propagation. Upon recognition of pathogen-associated molecular patterns (PAMPs) by cellular pattern recognition receptors (PRRs), numerous signaling cascades are activated, leading to the production of interferons (IFNs). IFNs act in an autocrine and paracrine manner to establish an antiviral state by inducing the expression of hundreds of IFN-stimulated genes (ISGs). Some of these ISGs are known to restrict bunyavirus infection. Along with other constitutively expressed host cellular factors with antiviral activity, these proteins (hereafter referred to as “restriction factors”) target different steps of the viral cycle, including viral entry, genome transcription and replication, and virion egress. In reaction to this, bunyaviruses have developed strategies to circumvent this antiviral response, by avoiding cellular recognition of PAMPs, inhibiting IFN production or interfering with the IFN-mediated response. Herein, we review the current knowledge on host cellular factors that were shown to restrict infections by bunyaviruses. Moreover, we focus on the strategies developed by bunyaviruses in order to escape the antiviral state developed by the infected cells.

NO Network for Plant-Microbe Communication Underground: A Review.

Mechanisms governing plant–microbe interaction in the rhizosphere attracted a lot of investigative attention in the last decade. The rhizosphere is not simply a source of nutrients and support for the plants; it is rather an ecosystem teeming with diverse flora and fauna including different groups of microbes that are useful as well as harmful for the plants. Plant–microbe interaction occurs via a highly complex communication network that involves sophisticated machinery for the recognition of friend and foe at both sides. On the other hand, nitric oxide (NO) is a key, signaling molecule involved in plant development and defense. Studies on legume–rhizobia symbiosis suggest the involvement of NO during recognition, root hair curling, development of infection threads, nodule development, and nodule senescence. A similar role of NO is also suggested in the case of plant interaction with the mycorrhizal fungi. Another, insight into the plant–microbe interaction in the rhizosphere comes from the recognition of pathogen-associated molecular patterns (PAMPs)/microbe-associated molecular patterns (MAMPs) by the host plant and thereby NO-mediated activation of the defense signaling cascade. Thus, NO plays a major role in mediating the communication between plants and microbes in the rhizosphere. Interestingly, reports suggesting the role of silicon in increasing the number of nodules, enhancing nitrogen fixation, and also the combined effect of silicon and NO may indicate a possibility of their interaction in mediating microbial communication underground. However, the exact role of NO in mediating plant–microbe interaction remains elusive. Therefore, understanding the role of NO in underground plant physiology is very important, especially in relation to the plant’s interaction with the rhizospheric microbiome. This will help devise new strategies for protection against phytopathogens and enhancing plant productivity by promoting symbiotic interaction. This review focuses on the role of NO in plant–microbe communication underground.

Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.

The complement system was discovered at the end of the 19th century as a heat-labile plasma component that “complemented” the antibodies in killing microbes, hence the name “complement.” Complement is also part of the innate immune system, protecting the host by recognition of pathogen-associated molecular patterns. However, complement is multifunctional far beyond infectious defense. It contributes to organ development, such as sculpting neuron synapses, promoting tissue regeneration and repair, and rapidly engaging and synergizing with a number of processes, including hemostasis leading to thromboinflammation. Complement is a double-edged sword. Although it usually protects the host, it may cause tissue damage when dysregulated or overactivated, such as in the systemic inflammatory reaction seen in trauma and sepsis and severe coronavirus disease 2019 (COVID-19). Damage-associated molecular patterns generated during ischemia-reperfusion injuries (myocardial infarction, stroke, and transplant dysfunction) and in chronic neurologic and rheumatic disease activate complement, thereby increasing damaging inflammation. Despite the long list of diseases with potential for ameliorating complement modulation, only a few rare diseases are approved for clinical treatment targeting complement. Those currently being efficiently treated include paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, and neuromyelitis optica spectrum disorders. Rare diseases, unfortunately, preclude robust clinical trials. The increasing evidence for complement as a pathogenetic driver in many more common diseases suggests an opportunity for future complement therapy, which, however, requires robust clinical trials; one ongoing example is COVID-19 disease. The current review aims to discuss complement in disease pathogenesis and discuss future pharmacological strategies to treat these diseases with complement-targeted therapies.Significance StatementThe complement system is the host’s defense friend by protecting it from invading pathogens, promoting tissue repair, and maintaining homeostasis. Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host’s enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.

Genome-wide transcriptome reveals mechanisms underlying Rlm1-mediated blackleg resistance on canola

Genetic resistance to blackleg (Leptosphaeria maculans, Lm) of canola (Brassica napus, Bn) has been extensively studied, but the mechanisms underlying the host–pathogen interaction are still not well understood. Here, a comparative transcriptome analysis was performed on a resistant doubled haploid Bn line carrying the resistance gene Rlm1 following inoculation with a virulent (avrLm1) or avirulent (AvrLm1) Lm isolate on cotyledons. A total of 6999 and 3015 differentially expressed genes (DEGs) were identified, respectively, in inoculated local tissues with compatible (susceptible) and incompatible (resistant) interactions. Functional enrichment analysis found several biological processes, including protein targeting to membrane, ribosome and negative regulation of programmed cell death, were over-represented exclusively among up-regulated DEGs in the resistant reaction, whereas significant enrichment of salicylic acid (SA) and jasmonic acid (JA) pathways observed for down-regulated DEGs occurred only in the susceptible reaction. A heat-map analysis showed that both biosynthesis and signaling of SA and JA were induced more significantly in the resistant reaction, implying that a threshold level of SA and JA signaling is required for the activation of Rlm1-mediated resistance. Co-expression network analysis revealed close correlation of a gene module with the resistance, involving DEGs regulating pathogen-associated molecular pattern recognition, JA signaling and transcriptional reprogramming. Substantially fewer DEGs were identified in mock-inoculated (control) cotyledons, relative to those in inoculated local tissues, including those involved in SA pathways potentially contributing to systemic acquired resistance (SAR). Pre-inoculation of cotyledon with either an avirulent or virulent Lm isolate, however, failed to induce SAR on remote tissues of same plant despite elevated SA and PR1 protein. This study provides insights into the molecular mechanism of Rlm1-mediated resistance to blackleg.

Novel TLR2xTLR4 Bispecific Antibody Inhibits Bacterial Sepsis.

Toll-like receptors (TLRs) sense microbial infection through recognition of pathogen-associated molecular patterns. For example, TLR4 responds to the lipopolysaccharide of gram-negative bacteria, whereas TLR2 recognizes a broad range of microbial ligands. Both receptors are, therefore, compelling targets for treating sepsis. Here, we developed a TLR2xTLR4 tetravalent bispecific antibody designated ICU-1, which inhibits both receptors. The inhibitory activity of ICU-1 was comparable to that of the parental antibodies in neutralization assays using a human monocyte cell line. Moreover, ICU-1 completely blocked stimulation of human peripheral blood mononuclear cells by clinically relevant bacterial species. These findings provide convincing evidence that ICU-1 offers a novel approach for treating bacterial sepsis.

Evaluation of IL-17D in Host Immunity to Group A Streptococcus Infection.

IL-17D is a cytokine that belongs to the IL-17 family and is conserved in vertebrates and invertebrates. In contrast to IL-17A and IL-17F, which are expressed in Th17 cells, IL-17D is expressed broadly in nonimmune cells. IL-17D can promote immune responses to cancer and viruses in part by inducing chemokines and recruiting innate immune cells such as NK cells. Although bacterial infection can induce IL-17D in fish and invertebrates, the role of mammalian IL-17D in antibacterial immunity has not been established. To determine whether IL-17D has a role in mediating host defense against bacterial infections, we studied i.p. infection by group A Streptococcus (GAS) in wild-type (WT) and Il17d -/- mice. Compared with WT animals, mice deficient in IL-17D experienced decreased survival, had greater weight loss, and showed increased bacterial burden in the kidney and peritoneal cavity following GAS challenge. In WT animals, IL-17D transcript was induced by GAS infection and correlated to increased levels of chemokine CCL2 and greater neutrophil recruitment. Of note, GAS-mediated IL-17D induction in nonimmune cells required live bacteria, suggesting that processes beyond recognition of pathogen-associated molecular patterns were required for IL-17D induction. Based on our results, we propose a model in which nonimmune cells can discriminate between nonviable and viable GAS cells, responding only to the latter by inducing IL-17D.

Molecular characterization of HEXOKINASE1 in plant innate immunity

Hexokinase1 (HXK1) is an Arabidopsis glucose sensor that has a variety of roles during plant growth and devlopment, including during germination, flowering, and senescence. HXK1 also acts as a positive regulator of plant immune responses. Previous research suggested that HXK1 might influence plant immune responses via responses to glucose. Plant immune responses are governed by two main pathways: PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI). PTI involves the recognition of Pathogen-Associated Molecular Patterns (PAMPs) and leads to increased callose formation and accumulation of pathogenesis response (PR) proteins. ETI acts in response to effectors secreted by Gram-negative bacteria. During ETI, the membrane-localized protein RPM1-interacting protein 4 (RIN4) becomes phosphorylated in reponse to interactions with effectors and mediates the downstream response. In this study, the effects of glucose on plant immune responses against infection with Pseudomonas syringae pv. tomato DC3000 and other P. syringae strains were investigated in the presence and absence of HXK1. Infiltration of leaves with glucose prior to infection led to decreases in bacterial populations and reductions in disease symptoms in wild-type Arabidopsis plants, indicating that glucose plays a role in plant immunity. Both PTI and ETI responses were affected. However, these effects were not observed in a hxk1 mutant, indicating that the effects of glucose on plant immune responses were mediated by HXK1-related pathways.

Transcriptome analysis reveals immune pathways underlying resistance in the common carp Cyprinus carpio against the oomycete Aphanomyces invadans

Infection with Aphanomyces invadans is a serious fish disease with major global impacts. Despite affecting over 160 fish species, some of the species like the common carp Cyprinus carpio are resistant to A. invadans infection. In the present study, we investigated the transcriptomes of head kidney of common carp experimentally infected with A. invadans. In time course analysis, 5288 genes were found to be differentially expressed (DEGs), of which 731 were involved in 21 immune pathways. The analysis of immune-related DEGs suggested that efficient processing and presentation of A. invadans antigens, enhanced phagocytosis, recognition of pathogen-associated molecular patterns, and increased recruitment of leukocytes to the sites of infection contribute to resistance of common carp against A. invadans. Herein, we provide a systematic understanding of the disease resistance mechanisms in common carp at molecular level as a valuable resource for developing disease management strategies for this devastating fish-pathogenic oomycete.

Intracellular PRRs Activation in Targeting the Immune Response Against Fungal Infections.

The immune response against fungal infections is complex and exhibits several factors involving innate elements that participate in the interaction with the fungus. The innate immune system developed pattern recognition receptors that recognize different pathogen-associated molecular patterns present both on the surface of the fungi cell wall and on their genetic material. These receptors have the function of activating the innate immune response and regulating a subsequent adaptive immune response. Among pattern recognition receptors, the family of Toll-like receptors and C-type lectin receptors are the best described and characterized, they act directly in the recognition of pathogen-associated molecular patterns expressed on the wall of the fungus and consequently in directing the immune response. In recent years, the role of intracellular pattern recognition receptors (TLR3, TLR7, TLR8, and TLR9) has become increasingly important in the pathophysiology of some mycoses, as paracoccidioidomycosis, cryptococcosis, aspergillosis, and candidiasis. The recognition of nucleic acids performed by these receptors can be essential for the control of some fungal infections, as they can be harmful to others. Therefore, this review focuses on highlighting the role played by intracellular pattern recognition receptors both in controlling the infection and in the host's susceptibility against the main fungi of medical relevance.

Molecular aspects of basic innate immunity in Hordeum vulgare L.

Basic innate immunity in plants is achieved via interactions between highly conserved pathogen-associated molecular structures and plant pattern recognition receptors, leading to elicitation of signaling cascades triggering molecular and cell defense mechanisms. At present, most of the components of basic innate immunity in barley have not been identified yet. Here, an overview of current knowledge on mechanisms underlying innate immunity in cereals is presented, based mostly on the data obtained for representatives of Triticeae and Oryzaeae, with a focus on the relationship between immunity, induction of autophagy and elicitation of programmed cell death during the defense response in barley.

The Structural Basis of IRF-3 Activation upon Phosphorylation.

The innate immune system is the first line of defense against bacterial and viral infections. The recognition of pathogen-associated molecular patterns by the RIG-I-like receptors, TLRs, and cGAS leads to the induction of IFN-I by activating the transcription factor IRF-3. Although the mechanism of IRF-3 activation has been extensively studied, the structural basis of IRF-3 activation upon phosphorylation is not fully understood. In this study, we determined the crystal structures of phosphorylated human and mouse IRF-3 bound to CREB-binding protein (CBP), which reveal that phosphorylated IRF-3 forms a dimer via pSer386 (pSer379 in mouse IRF-3) and a downstream pLxIS motif. Size-exclusion chromatography and cell-based studies show that mutations of key residues interacting with pSer386 severely impair IRF-3 activation and IFN-β induction. By contrast, phosphorylation of Ser396 within the pLxIS motif of human IRF-3 only plays a moderate role in IRF-3 activation. The mouse IRF-3/CBP complex structure reveals that the mechanism of mouse IRF-3 activation is similar but distinct from human IRF-3. These structural and functional studies reveal the detailed mechanism of IRF-3 activation upon phosphorylation.

Fungal recognition by mammalian fibrinogen-related proteins.

Fungi are ubiquitous eukaryotic micro-organisms present in virtually all environmental habitats. Although rarely pathogenic to the healthy population, many fungal species are capable of causing human disease in immunocompromised individuals. Thus, fungal infections remain a significant cause of morbidity and mortality, with rising prevalence accompanying the worldwide increase in immunosuppression-based therapies. Therefore, better understanding of the mutual interactions between the protective host mechanisms and the invading fungi remains of critical importance. The innate immune system constitutes the first line of defence against exogenous insults. The innate antifungal immunity is mediated through recognition of specific pathogen-associated molecular patterns (PAMPs) by a broad panel of host pattern recognition receptors (PRRs), responsible for mounting adequate protective responses. In this review, we describe fungal PAMPs as well as a selection of PRRs able to recognize them. We focus on the members of the fibrinogen-related domain (FReD) protein family that have been shown to recognize fungi-derived molecules: ficolins, fibrinogen C domain containing 1 (FIBCD1) and tenascin-C. We describe their structure, their binding targets and their established as well as putative biological functions related to fungal recognition and immunity.

Effect of bacterial LPS, poly I:C and temperature on the immune response of coelomocytes in short term cultures of red sea urchin (Loxechinus albus)

In echinoderms, the immune system plays a relevant role in defense against infection by pathogens. Particularly, in sea urchins, the immune system has been shown to be complex, especially in terms of the variety of immune genes and molecules described. A key component of the response to external pathogens are the Toll-like receptors (TLRs), which are a well-characterized class of pattern recognition receptors (PRRs) that participate in the recognition of pathogen-associated molecular patterns (PAMPs). Despite the fact that TLRs have been described in several sea urchin species, for the red sea urchin (Loxechinus albus), which is one of the most important sea urchins across the world in terms of fisheries, limited information on the TLR-mediated immune response exists. In the present study, for the first time, we evaluated the effect of thermal stress, LPS and poly I:C treatment on the coelomocyte immune response of Loxechinus albus to determine how these factors modulate TLR and strongylocin (antimicrobial peptides of echinoderms) responses. We show that the tlr3-like, tlr4-like, tlr6-like and tlr8-like transcripts are modulated by poly I:C, while LPS only modulates the tlr4-like response; there was no effect of temperature on TLR expression, as evaluated by RT-qPCR. Additionally, we showed that strongylocin-1 and strongylocin-2 are modulated in response to simulated viral infection with poly I:C, providing the first evidence of strongylocin expression in L. albus. Finally, we determined that temperature and LPS modify the viability of coelomocytes, while poly I:C treatment did not affect the viability of these cells. This study contributes to the knowledge of immune responses in sea urchins to improve the understanding of the role of TLRs and strongylocins in echinoderms.

In Vitro Activation of Macrophages by an MHC Class II-restricted Trichomonas Vaginalis TvZIP8-derived Synthetic Peptide

ABSTRACT Background Macrophages play an important role in the inflammatory response towards pathogens and their effector functions depend on the mode of activation which is mediated by recognition of pathogen-associated molecular patterns, as peptides. Trichomonas vaginalis provokes an inflammatory response in the host in which macrophages are the first line of defense. This study aimed to analyze the effect of a specific peptide derived from the transporter TvZIP8 of T. vaginalis on the activation of macrophages. Methods An in silico approach based on computational prediction of epitopes was applied to detect potential murine MHC class II-restricted peptides from TvZIP8 that can activate macrophages and the immunomodulatory activity was evaluated by in vitro stimulation of murine macrophages. Results Based on binding scores, one peptide denominated TvZIP8-pep was selected for further analysis. In vitro stimulation with synthetic TvZIP8-pep triggered on murine macrophages the NO and H2O2 production and an overexpression of iNOS and NOX-2 genes. Also, a significant increase of pro-inflammatory cytokines: IL-1β, IL-6, and TNF-α, as well as, overexpression of the TLR4, MyD88, and NF-κB genes and NF-κB activation were observed on macrophages after stimulation with TvZIP8-pep in vitro. Moreover, higher levels of IFN-γ were detected in co-cultures using CD4 + T cells with TvZIP8-pep-stimulated macrophages Conclusion These results support the potential of TvZIP8 as a promising antigen to stimulates a specific macrophage response against T. vaginalis, but further analyses are required to evaluate their possible potential as a novel antigen for immunodiagnosis and/or vaccine against trichomoniasis.

Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease.

Liver sinusoidal endothelial cells (LSECs) are the most abundant non-parenchymal cells lining the sinusoidal capillaries of the hepatic system. LSECs are characterized with numerous fenestrae and lack basement membrane as well as a diaphragm. These unique morphological characteristics of LSECs makes them the most permeable endothelial cells of the mammalian vasculature and aid in regulating flow of macromolecules and small lipid-based structures between sinusoidal blood and parenchymal cells. LSECs have a very high endocytic capacity aided by scavenger receptors (SR), such as SR-A, SR-B (SR-B1 and CD-36), SR-E (Lox-1 and mannose receptors), and SR-H (Stabilins). Other high-affinity receptors for mediating endocytosis include the FcγRIIb, which assist in the antibody-mediated removal of immune complexes. Complemented with intense lysosomal activity, LSECs play a vital role in the uptake and degradation of many blood borne waste macromolecules and small (<280 nm) colloids. Currently, seven Toll-like receptors have been investigated in LSECs, which are involved in the recognition and clearance of pathogen-associated molecular pattern (PAMPs) as well as damage associated molecular pattern (DAMP). Along with other SRs, LSECs play an essential role in maintaining lipid homeostasis with the low-density lipoprotein receptor-related protein-1 (LRP-1), in juxtaposition with hepatocytes. LSECs co-express two surface lectins called L-Specific Intercellular adhesion molecule-3 Grabbing Non-integrin Receptor (L-SIGN) and liver sinusoidal endothelial cell lectin (LSECtin). LSECs also express several adhesion molecules which are involved in the recruitment of leukocytes at the site of inflammation. Here, we review these cell surface receptors as well as other components expressed by LSECs and their functions in the maintenance of liver homeostasis. We further discuss receptor expression and activity and dysregulation associated with the initiation and progression of many liver diseases, such as hepatocellular carcinoma, liver fibrosis, and cirrhosis, alcoholic and non-alcoholic fatty liver diseases and pseudocapillarization with aging.

ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1.

The innate immune response constitutes the first line of defense against pathogens. It involves the recognition of pathogen-associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs), the production of inflammatory cytokines and the recruitment of immune cells to infection sites. Recently, ADP-heptose, a soluble intermediate of the lipopolysaccharide biosynthetic pathway in Gram-negative bacteria, has been identified by several research groups as a PAMP. Here, we recapitulate the evidence that led to this identification and discuss the controversy over the immunogenic properties of heptose 1,7-bisphosphate (HBP), another bacterial heptose previously defined as an activator of innate immunity. Then, we describe the mechanism of ADP-heptose sensing by alpha-protein kinase 1 (ALPK1) and its downstream signaling pathway that involves the proteins TIFA and TRAF6 and induces the activation of NF-κB and the secretion of inflammatory cytokines. Finally, we discuss possible delivery mechanisms of ADP-heptose in cells during infection, and propose new lines of thinking to further explore the roles of the ADP-heptose/ALPK1/TIFA axis in infections and its potential implication in the control of intestinal homeostasis.

Contribution of Aberrant Toll Like Receptor Signaling to the Pathogenesis of Myelodysplastic Syndromes.

Toll like receptors (TLRs) are a family of pattern recognition receptors that play a central role in the innate immune response. These receptors are expressed on a wide variety of immune and non-immune cells, and they help shape the immune response to infection and injury through the recognition of pathogen-associated molecular patterns (PAMPs) as well as endogenous damage-associated molecular patterns (DAMPs). Accumulating evidence suggests that, in addition to regulating mature effector immune cells, TLRs can influence the immune response from the level of the hematopoietic stem cell (HSC). HSCs express TLRs, and exposure to TLR ligands influences the cycling, differentiation, and function of HSCs, with chronic TLR stimulation leading to impairment of normal HSC repopulating activity. Moreover, enhanced TLR expression and signaling is associated with myelodysplastic syndromes (MDS), a heterogenous group of HSC disorders characterized by ineffective hematopoiesis and a high risk of transformation to acute leukemias. In this review, we will discuss the role of TLR signaling in the pathogenesis of MDS, focusing on the known direct and indirect effects of this type of signaling on HSCs, the mechanisms of TLR signaling upregulation in MDS, the changes in TLR expression with disease progression, and the therapeutic implications for modulating TLR signaling in the treatment of MDS.

The Evolution of Dendritic Cell Immunotherapy against HIV-1 Infection: Improvements and Outlook.

Dendritic cells (DC) are key phagocytic cells that play crucial roles in both the innate and adaptive immune responses against the human immunodeficiency virus type 1 (HIV-1). By processing and presenting pathogen-derived antigens, dendritic cells initiate a directed response against infected cells. They activate the adaptive immune system upon recognition of pathogen-associated molecular patterns (PAMPs) on infected cells. During the course of HIV-1 infection, a successful adaptive (cytotoxic CD8+ T-cell) response is necessary for preventing the progression and spread of infection in a variety of cells. Dendritic cells have thus been recognized as a valuable tool in the development of immunotherapeutic approaches and vaccines effective against HIV-1. The advancements in dendritic cell vaccines in cancers have paved the way for applications of this form of immunotherapy to HIV-1 infection. Clinical trials with patients infected with HIV-1 who are well-suppressed by antiretroviral therapy (ART) were recently performed to assess the efficacy of DC vaccines, with the goal of mounting an HIV-1 antigen-specific T-cell response, ideally to clear infection and eliminate the need for long-term ART. This review summarizes and compares methods and efficacies of a number of DC vaccine trials utilizing autologous dendritic cells loaded with HIV-1 antigens. The potential for advancement and novel strategies of improving efficacy of this type of immunotherapy is also discussed.

The immunology of COVID-19: is immune modulation an option for treatment?

SummaryIn December, 2019, an outbreak of COVID-19 emerged in Wuhan, China and quickly spread globally. As of May 7, 2020, there were 3 672 238 confirmed infections and 254 045 deaths attributed to COVID-19. Evidence has shown that there are asymptomatic carriers of COVID-19 who can transmit the disease to others. The virus incubation time shows a wide range (0–24 days) and the virus displays a high infectivity. It is therefore urgent to develop an effective therapy to treat patients with COVID-19 and to control the spread of the causative agent, severe respiratory syndrome coronavirus 2. Repurposing of approved drugs is widely adopted to fight newly emerged diseases such as COVID-19, as these drugs have known pharmacokinetic and safety profiles. As pathological examination has confirmed the involvement of immune hyperactivation and acute respiratory distress syndrome in fatal cases of COVID-19, several disease-modifying anti-rheumatic drugs (DMARDS), such as hydroxychloroquine and tocilizumab, have been proposed as potential therapies for the treatment of COVID-19. In this Review, we discuss the immunological aspects of COVID-19 and the potential implication of DMARDs in treating this disease.