NLR immune receptor-nanobody fusions confer plant disease resistance.

Plant pathogens cause recurrent epidemics, threatening crop yield and global food security. Efforts to retool the plant immune system have been limited to modifying natural components and can be nullified by the emergence of new pathogen strains. Made-to-order synthetic plant immune receptors provide an opportunity to tailor resistance to pathogen genotypes present in the field. In this work, we show that plant nucleotide-binding, leucine-rich repeat immune receptors (NLRs) can be used as scaffolds for nanobody (single-domain antibody fragment) fusions that bind fluorescent proteins (FPs). These fusions trigger immune responses in the presence of the corresponding FP and confer resistance against plant viruses expressing FPs. Because nanobodies can be raised against most molecules, immune receptor-nanobody fusions have the potential to generate resistance against plant pathogens and pests delivering effectors inside host cells.

Seronegative MSM at high risk of HIV-1 acquisition show an immune quiescent profile with a normal immune response against common antigens.

Human immunodeficiency virus (HIV) infection still represents a major public health problem worldwide, and its vaccine remains elusive. The study of HIV-exposed seronegative individuals (HESN) brings important information about the natural resistance to HIV, allows a better understanding of the infection, and opens doors for new preventive and therapeutic strategies. Among HESN groups, there are some men who have sex with men (MSM) with high-risk sexual behaviors, who represent an adequate cohort for HESN study because of their major HIV exposure without infection. This study aimed to compare the immunological profile of Colombian seronegative MSM with different risk sexual behaviors. This study included 60 MSM at high-risk (n = 16) and low-risk (n = 44) of HIV-1 acquisition. No sex worker nor homozygous delta 32 mutation subjects were included. All participants were negative for anti-HIV-1/2 antibodies and HIV-1 proviral DNA. A higher frequency of sexual partners in the last 3 months before the study participation (median, 30 vs. 2), lifetime sexual partners (median, 1,708 vs. 26), and unprotected anal intercourse (median 12.5 vs. 2) was determined in high-risk MSM than low-risk MSM. High-risk MSM also showed a quiescent profile of T cells and natural killer (NK) cells, with a significantly lower percentage of CD4+CD38+, CD4+HLADR-CD38+, CD4+Ki67+ T cells, and NKG2D+ NK cells (CD3-CD16+CD56+), a significantly higher percentage of CD4+HLADR-CD38-, and a tendency to show a higher percentage of CD8+HLADR+CD38- T cells than the low-risk group. Likewise, they showed higher mRNA levels of Serpin A1 from PBMCs. The results suggest that this MSM cohort could be HESN individuals and their resistance would be explained by a quiescent profile of T cells and NK cells and an increased Serpin A1 expression. Further study on MSM at high risk of exposure to HIV-1 is necessary to better understand the natural resistance to HIV.

Immunity to SARS-CoV-2: What Do We Know and Should We Be Testing for It?

Preexisting immunity to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was nonexistent in humans, which coupled with high transmission rates of certain SARS-CoV-2 variants and limited vaccine uptake or availability, has collectively resulted in an ongoing global pandemic. The identification and establishment of one or multiple correlates of protection (CoP) against infectious pathogens is challenging, but beneficial from both the patient care and public health perspectives. Multiple studies have shown that neutralizing antibodies, whether generated following SARS-CoV-2 infection, vaccination, or a combination of both (i.e., hybrid immunity), as well as adaptive cellular immune responses, serve as CoPs for COVID-19. However, the diverse number and type of serologic assays, alongside the lack of cross-assay standardization and emergence of new SARS-CoV-2 variants with immune evasive characteristics, have collectively posed challenges to determining a robust CoP 'threshold' and for the routine utilization of these assays to document 'immunity,' as is commonly done for other vaccine preventable diseases. Here, we discuss what CoPs are, review our current understanding of infection-induced, vaccine-elicited and hybrid immunity to COVID-19 and summarize the current and potential future utility of SARS-CoV-2 serologic testing.

Innate Immune Memory and the Host Response to Infection.

Unlike the adaptive immune system, the innate immune system has classically been characterized as being devoid of memory functions. However, recent research shows that innate myeloid and lymphoid cells have the ability to retain memory of prior pathogen exposure and become primed to elicit a robust, broad-spectrum response to subsequent infection. This phenomenon has been termed innate immune memory or trained immunity. Innate immune memory is induced via activation of pattern recognition receptors and the actions of cytokines on hematopoietic progenitors and stem cells in bone marrow and innate leukocytes in the periphery. The trained phenotype is induced and sustained via epigenetic modifications that reprogram transcriptional patterns and metabolism. These modifications augment antimicrobial functions, such as leukocyte expansion, chemotaxis, phagocytosis, and microbial killing, to facilitate an augmented host response to infection. Alternatively, innate immune memory may contribute to the pathogenesis of chronic diseases, such as atherosclerosis and Alzheimer's disease.

Plant immunity: Rice XA21-mediated resistance to bacterial infection.

In this article, we describe the development of the plant immunity field, starting with efforts to understand the genetic basis for disease resistance, which ∼30 y ago led to the discovery of diverse classes of immune receptors that recognize and respond to infectious microbes. We focus on knowledge gained from studies of the rice XA21 immune receptor that recognizes RaxX (required for activation of XA21 mediated immunity X), a sulfated microbial peptide secreted by the gram-negative bacterium Xanthomonas oryzae pv. oryzae. XA21 is representative of a large class of plant and animal immune receptors that recognize and respond to conserved microbial molecules. We highlight the complexity of this large class of receptors in plants, discuss a possible role for RaxX in Xanthomonas biology, and draw attention to the important role of sulfotyrosine in mediating receptor-ligand interactions.

Genotyping-by-sequencing-based QTL mapping reveals novel loci for Pepper yellow leaf curl virus (PepYLCV) resistance in Capsicum annuum.

Disease caused by Pepper yellow leaf curl virus (PepYLCV) is one of the greatest threats to pepper (Capsicum spp.) cultivation in the tropics and subtropics. Resistance to PepYLCV was previously identified in a few Capsicum accessions, but no resistance QTLs have been mapped. This study aimed to elucidate the genetics of PepYLCV resistance in C. annuum L. Augmented inoculation by the viruliferous whitefly Bemisia tabaci was used to evaluate parental lines and an F2 segregating population derived from a cross between resistant C. annuum line LP97 and susceptible C. annuum line ECW30R. Final evaluation was performed six weeks after inoculation using a standardized 5-point scale (0 = no symptoms to 4 = very severe symptoms). A high-density linkage map was constructed using genotyping-by-sequencing (GBS) to identify single-nucleotide polymorphism (SNP) markers associated with PepYLCV resistance in the F2 population. QTL analysis revealed three QTLs, peplcv-1, peplcv-7, and peplcv-12, on chromosomes P1, P7, and P12, respectively. Candidate genes associated with PepYLCV resistance in the QTL regions were inferred. In addition, single markers Chr7-LCV-7 and Chr12-LCV-12 derived from the QTLs were developed and validated in another F2 population and in commercial varieties. This work thus provides not only information for mapping PepYLCV resistance loci in pepper but also forms the basis for future molecular analysis of genes involved in PepYLCV resistance.

Identification of a Pm4 Allele as a Powdery Mildew Resistance Gene in Wheat Line Xiaomaomai.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive foliar diseases of wheat. In this study, we combined the bulked segregant RNA sequencing (BSR-seq) and comparative genomics analysis to localize the powdery mildew resistance gene in Chinese landrace Xiaomaomai. Genetic analysis of F1 plants from a crossing of Xiaomaomai × Lumai23 and the derived F2 population suggests that a single recessive gene, designated as pmXMM, confers the resistance in this germplasm. A genetic linkage map was constructed using the newly developed SNP markers and pmXMM was mapped to the distal end of chromosome 2AL. The two flanking markers 2AL15 and 2AL34 were closely linked to pmXMM at the genetic distance of 3.9 cM and 1.4 cM, respectively. Using the diagnostic primers of Pm4, we confirmed that Xiaomaomai carries a Pm4 allele and the gene function was further validated by the virus-induced gene silencing (VIGS). In addition, we systematically analyzed pmXMM in comparison with the other Pm4 alleles. The results suggest that pmXMM is identical to Pm4d and Pm4e at sequence level. Pm4b is also not different from Pm4c according to their genome/amino acid sequences. Only a few nucleotide variances were detected between pmXMM and Pm4a/b, which indicate the haplotype variation of the Pm4 gene.

Identification of a novel stripe rust resistance gene from the European winter wheat cultivar 'Acienda': A step towards rust proofing wheat cultivation.

All stage resistance to stripe rust races prevalent in India was investigated in the European winter wheat cultivar 'Acienda'. In order to dissect the genetic basis of the resistance, a backcross population was developed between 'Acienda' and the stripe rust susceptible Indian spring wheat cultivar 'HD 2967'. Inheritance studies revealed segregation for a dominant resistant gene. High density SNP genotyping was used to map stripe rust resistance and marker regression analysis located stripe rust resistance to the distal end of wheat chromosome 1A. Interval mapping located this region between the SNP markers AX-95162217 and AX-94540853, at a LOD score of 15.83 with a phenotypic contribution of 60%. This major stripe rust resistance locus from 'Acienda' has been temporarily designated as Yraci. A candidate gene search in the 2.76 Mb region carrying Yraci on chromosome 1A identified 18 NBS-LRR genes based on wheat RefSeqv1.0 annotations. Our results indicate that as there is no major gene reported in the Yraci chromosome region, it is likely to be a novel stripe rust resistance locus and offers potential for deployment, using the identified markers, to confer all stage stripe rust resistance.

Monocyte Gene and Molecular Expression Profiles Suggest Distinct Effector and Regulatory Functions in Beninese HIV Highly Exposed Seronegative Female Commercial Sex Workers.

We have previously reported that the female genital tract (FGT) of Beninese HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs), presented elevated frequencies of a myeloid HLA-DR+CD14+CD11c+ population presenting "tolerogenic" monocyte derived dendritic cells (MoDC) features. In order to assess whether a differential profile of monocytes may be involved in the generation of these genital MoDCs, we have herein characterized the blood monocyte compartment of Beninese HESNs (HIV-uninfected ≥ 10 years CSWs) and relevant controls (HIV-uninfected 2.5-5 years CSWs herein termed "early HESNs"), HIV-infected CSWs, and low-risk HIV-uninfected women from the general population. Transcriptomic analyses by RNA-Seq of total sorted blood monocytes demonstrate that in comparison to the control groups, HESNs present increased expression levels of FCGR2C, FCAR, ITGAX, ITGAM, CR2, CD68, and CD163 genes, associated with effector functions. Moreover, we found increased expression levels of genes associated with protection/control against SHIV/HIV such as CCL3, CCL4, CCL5, BHLHE40, and TNFSF13, as well as with immune regulation such as IL-10, Ahr, CD83, and the orphan nuclear receptor (NR)4A1, NR4A2, and NR4A3. Through multicolor flow cytometry analyses, we noticed that the frequencies of intermediate and non-classical monocyte populations tended to be elevated in the blood of HESNs, and exhibited increased expression levels of effector CD16, CD11c, CD11b, as well as regulatory HLA-G, IL-10, and IFN-α markers when compared to HIV-uninfected women and/or HIV-infected CSWs. This profile is compatible with that previously reported in the FGT of HESNs, and likely confers an enormous advantage in their resistance to HIV infection.

The Protein Phosphatase GhAP2C1 Interacts Together with GhMPK4 to Synergistically Regulate the Immune Response to Fusarium oxysporum in Cotton.

The plant mitogen-activated protein kinase (MAPK) cascade plays an important role in mediating responses to biotic and abiotic stresses and is the main pathway through which extracellular stimuli are transduced intracellularly as signals. Our previous research showed that the GhMKK6-GhMPK4 cascade signaling pathway plays an important role in cotton immunity. To further analyze the role and regulatory mechanism of the GhMKK6-GhMPK4 cascade signaling pathway in cotton resistance to Fusarium wilt, we functionally analyzed GhMPK4. Our results show that silencing GhMPK4 reduces cotton tolerance to Fusarium wilt and reduces the expression of several resistance genes. Further experiments revealed that GhMPK4 is similar to GhMKK6, both of whose overexpression cause unfavorable cotton immune response characteristics. By using a yeast two-hybrid screening library and performing a bioinformatics analysis, we screened and identified a negative regulator of the MAPK kinase-protein phosphatase AP2C1. Through the functional analysis of AP2C1, it was found that, after being silenced, GhAP2C1 increased resistance to Fusarium wilt, but GhAP2C1 overexpression caused sensitivity to Fusarium wilt. These findings show that GhAP2C1 interacts together with GhMPK4 to regulate the immune response of cotton to Fusarium oxysporum, which provides important data for functionally analyzing and studying the feedback regulatory mechanism of the MAPK cascade and helps to clarify the regulatory mechanism through which the MAPK cascade acts in response to pathogens.

Integrated Transcriptome and Metabolome Analysis Reveals Key Metabolites Involved in Camellia oleifera Defense against Anthracnose.

Camellia oleifera (Ca. oleifera) is a woody tree species cultivated for the production of edible oil from its seed. The growth and yield of tea-oil trees are severely affected by anthracnose (caused by Colletotrichum gloeosporioides). In this study, the transcriptomic and metabolomic analyses were performed to detect the key transcripts and metabolites associated with differences in the susceptibility between anthracnose-resistant (ChangLin150) and susceptible (ChangLin102) varieties of Ca. oleifera. In total, 5001 differentially expressed genes (DEGs) were obtained, of which 479 DEGs were common between the susceptible and resistant varieties and further analyzed. KEGG enrichment analysis showed that these DEGs were significantly enriched in tyrosine metabolism, phenylpropanoid biosynthesis, flavonoid biosynthesis and isoquinoline alkaloid biosynthesis pathways. Furthermore, 68 differentially accumulated metabolites (DAMs) were detected, including flavonoids, such as epicatechin, phenethyl caffeate and procyanidin B2. Comparison of the DEGs and DAMs revealed that epicatechin, procyanidin B2 and arachidonic acid (peroxide free) are potentially important. The expression patterns of genes involved in flavonoid biosynthesis were confirmed by qRT-PCR. These results suggested that flavonoid biosynthesis might play an important role in the fight against anthracnose. This study provides valuable molecular information about the response of Ca. oleifera to Co. gloeosporioides infection and will aid the selection of resistant varieties using marker-assisted breeding.

ERF Transcription Factor OsBIERF3 Positively Contributes to Immunity against Fungal and Bacterial Diseases but Negatively Regulates Cold Tolerance in Rice.

We previously showed that overexpression of the rice ERF transcription factor gene OsBIERF3 in tobacco increased resistance against different pathogens. Here, we report the function of OsBIERF3 in rice immunity and abiotic stress tolerance. Expression of OsBIERF3 was induced by Xanthomonas oryzae pv. oryzae, hormones (e.g., salicylic acid, methyl jasmonate, 1-aminocyclopropane-1-carboxylic acid, and abscisic acid), and abiotic stress (e.g., drought, salt and cold stress). OsBIERF3 has transcriptional activation activity that depends on its C-terminal region. The OsBIERF3-overexpressing (OsBIERF3-OE) plants exhibited increased resistance while OsBIERF3-suppressed (OsBIERF3-Ri) plants displayed decreased resistance to Magnaporthe oryzae and X. oryzae pv. oryzae. A set of genes including those for PRs and MAPK kinases were up-regulated in OsBIERF3-OE plants. Cell wall biosynthetic enzyme genes were up-regulated in OsBIERF3-OE plants but down-regulated in OsBIERF3-Ri plants; accordingly, cell walls became thicker in OsBIERF3-OE plants but thinner in OsBIERF3-Ri plants than WT plants. The OsBIERF3-OE plants attenuated while OsBIERF3-Ri plants enhanced cold tolerance, accompanied by altered expression of cold-responsive genes and proline accumulation. Exogenous abscisic acid and 1-aminocyclopropane-1-carboxylic acid, a precursor of ethylene biosynthesis, restored the attenuated cold tolerance in OsBIERF3-OE plants while exogenous AgNO3, an inhibitor of ethylene action, significantly suppressed the enhanced cold tolerance in OsBIERF3-Ri plants. These data demonstrate that OsBIERF3 positively contributes to immunity against M. oryzae and X. oryzae pv. oryzae but negatively regulates cold stress tolerance in rice.

Plasmodium falciparum Cysteine-Rich Protective Antigen (CyRPA) Elicits Detectable Levels of Invasion-Inhibitory Antibodies during Natural Infection in Humans.

Plasmodium falciparum cysteine-rich protective antigen (CyRPA) is a conserved component of an essential erythrocyte invasion complex (RH5/Ripr/CyRPA) and a target of potent cross-strain parasite-neutralizing antibodies. While naturally acquired human RH5 antibodies have been functionally characterized, there are no similar reports on CyRPA. Thus, we analyzed the parasite-neutralizing activity of naturally acquired human CyRPA antibodies. In this regard, CyRPA human antibodies were measured and purified from malaria-infected plasma obtained from patients in central India and analyzed for their parasite neutralizing activity via in vitro growth inhibition assays (GIA). We report that, despite being susceptible to antibodies, CyRPA is a highly conserved antigen that does not appear to be under substantial immune selection pressure, as a very low acquisition rate for anti-CyRPA antibodies was reported in malaria-exposed Indians. We demonstrate for the first time that the small amounts of natural CyRPA antibodies exhibited functional parasite-neutralizing activity and that a CyRPA-based vaccine formulation induces highly potent antibodies in rabbits. Importantly, the vaccine-induced CyRPA antibodies exhibited a robust 50% inhibitory concentration (IC50) of 21.96 µg/ml, which is comparable to the IC50 of antibodies against the leading blood-stage vaccine candidate, reticulocyte-binding-like homologous protein 5 (RH5). Our data support CyRPA as a unique vaccine target that is highly susceptible to immune attack but is highly conserved compared to other leading candidates such as MSP-1 and AMA-1, further substantiating its promise as a leading blood-stage vaccine candidate.

The Intestinal Commensal, Bacteroides fragilis, Modulates Host Responses to Viral Infection and Therapy: Lessons for Exploration during Mycobacterium tuberculosis Infection.

The gut microbiota has emerged as a critical player in host health. Bacteroides fragilis is a prominent member of the gut microbiota within the phyla Bacteroidetes. This commensal bacterium produces unique capsular polysaccharides processed by antigen-presenting cells and activates CD4+ T cells to secrete inflammatory cytokines. Indeed, due to their immunomodulatory functions, B. fragilis and its capsular polysaccharide-A (PSA) are arguably the most explored single commensal microbiota/symbiotic factor. B. fragilis/PSA has been shown to protect against colitis, encephalomyelitis, colorectal cancer, pulmonary inflammation, and asthma. Here, we review recent data on the immunomodulatory role of B. fragilis/PSA during viral infections and therapy, B. fragilis PSA's dual ability to mediate pro-and anti-inflammatory processes, and the potential for exploring this unique characteristic during intracellular bacterial infections such as with Mycobacterium tuberculosis. We also discuss the protective roles of single commensal-derived probiotic species, including B. fragilis in lung inflammation and respiratory infections that may provide essential cues for possible exploration of microbiota based/augmented therapies in tuberculosis (TB). Available data on the relationship between B. fragilis/PSA, the immune system, and disease suggest clinical relevance for developing B. fragilis into a next-generation probiotic or, possibly, the engineering of PSA into a potent carbohydrate-based vaccine.

Long Noncoding RNA MIR2187HG Suppresses TBK1-Mediated Antiviral Signaling by Deriving miR-2187-3p in Teleost Fish.

Long noncoding RNAs (lncRNAs) function as microregulatory factors that influence gene expression after a variety of pathogenic infections, and they have been extensively studied in the past few years. Although less attention has been paid to lncRNAs in lower vertebrates than in mammals, current studies reveals that lncRNAs play a vital role in fish stimulated by pathogens. Here, we discovered a new lncRNA, termed MIR2187HG, which can function as a precursor of a small RNA, miR-2187-3p, with regulatory functions in the miiuy croaker (Miichthys miiuy). Upon Siniperca chuatsi rhabdovirus (SCRV) virus infection, the expression levels of MIR2187HG were remarkably enhanced. Elevated MIR2187HG expression can act as a pivotally negative regulator that participates in the innate immune response of teleost fish to inhibit the intracellular TANK-binding kinase 1 (TBK1)-mediated antiviral signaling pathways, which can effectively avoid excessive immunity. In addition, we found that SCRV could also utilize MIR2187HG to enhance its own numbers. Our results not only provide evidence regarding the involvement of the lncRNAs in response to viruses in fish but also broaden our understanding of the function of lncRNAs as precursor microRNAs (miRNAs) in teleost fish for the first time. IMPORTANCE SCRV infection upregulates MIR2187HG levels, which in turn suppresses SCRV-triggered type I interferon production, thus promoting viral replication in miiuy croaker. Notably, MIR2187HG regulates the release of miR-2187-3p, and TBK1 is a target of miR-2187-3p. MIR2187HG could acquire from miR-2187-3p the function of inhibiting TBK1 expression and subsequently modulate TBK1-mediated NF-κB and IRF3 signaling. The collective results suggest that the novel regulation mechanism of TBK1-mediated antiviral response during RNA viral infection was regulated by MIR2187HG. Therefore, a new regulation mechanism for lncRNAs to regulate antiviral immune responses in fish is proposed.

The Role of IFITM Proteins in Tick-Borne Encephalitis Virus Infection.

Tick-borne encephalitis virus (TBEV), of the genus Flavivirus, is a causative agent of severe encephalitis in regions of endemicity of northern Asia and central and northern Europe. Interferon-induced transmembrane proteins (IFITMs) are restriction factors that inhibit the replication cycles of numerous viruses, including flaviviruses such as West Nile virus, dengue virus, and Zika virus. Here, we demonstrate the role of IFITM1, IFITM2, and IFITM3 in the inhibition of TBEV infection and in protection against virus-induced cell death. We show that the most significant role is that of IFITM3, including the dissection of its functional motifs by mutagenesis. Furthermore, through the use of CRISPR-Cas9-generated IFITM1/3-knockout monoclonal cell lines, we confirm the role and additive action of endogenous IFITMs in TBEV suppression. However, the results of coculture assays suggest that TBEV might partially escape interferon- and IFITM-mediated suppression during high-density coculture infection when the virus enters naive cells directly from infected donor cells. Thus, cell-to-cell spread may constitute a strategy for virus escape from innate host defenses. IMPORTANCE TBEV infection may result in encephalitis, chronic illness, or death. TBEV is endemic in northern Asia and Europe; however, due to climate change, new centers of endemicity have arisen. Although effective TBEV vaccines have been approved, vaccination coverage is low, and due to the lack of specific therapeutics, infected individuals depend on their immune responses to control the infection. IFITM proteins are components of the innate antiviral defenses that suppress cell entry of many viral pathogens. However, no studies on the role of IFITM proteins in TBEV infection have been published thus far. Understanding antiviral innate immune responses is crucial for the future development of antiviral strategies. Here, we show the important role of IFITM proteins in the inhibition of TBEV infection and virus-mediated cell death. However, our data suggest that TBEV cell-to-cell spread may be less prone to both interferon- and IFITM-mediated suppression, potentially facilitating escape from IFITM-mediated immunity.

Phytophthora infestans RXLR effector Pi04089 perturbs diverse defense-related genes to suppress host immunity.

BACKGROUND: The oomycete pathogen secretes many effectors into host cells to manipulate host defenses. For the majority of effectors, the mechanisms related to how they alter the expression of host genes and reprogram defenses are not well understood. In order to investigate the molecular mechanisms governing the influence that the Phytophthora infestans RXLR effector Pi04089 has on host immunity, a comparative transcriptome analysis was conducted on Pi04089 stable transgenic and wild-type potato plants. RESULTS: Potato plants stably expressing Pi04089 were more susceptible to P. infestans. RNA-seq analysis revealed that 658 upregulated genes and 722 downregulated genes were characterized in Pi04089 transgenic lines. A large number of genes involved in the biological process, including many defense-related genes and certain genes that respond to salicylic acid, were suppressed. Moreover, the comparative transcriptome analysis revealed that Pi04089 significantly inhibited the expression of many flg22 (a microbe-associated molecular pattern, PAMP)-inducible genes, including various Avr9/Cf-9 rapidly elicited (ACRE) genes. Four selected differentially expressed genes (StWAT1, StCEVI57, StKTI1, and StP450) were confirmed to be involved in host resistance against P. infestans when they were transiently expressed in Nicotiana benthamiana. CONCLUSION: The P. infestans effector Pi04089 was shown to suppress the expression of many resistance-related genes in potato plants. Moreover, Pi04089 was found to significantly suppress flg22-triggered defense signaling in potato plants. This research provides new insights into how an oomycete effector perturbs host immune responses at the transcriptome level.

Type I Interferon and the Spectrum of Susceptibility to Viral Infection and Autoimmune Disease: A Shared Genomic Signature.

Type I interferons (IFN-I) and their cognate receptor, the IFNAR1/2 heterodimer, are critical components of the innate immune system in humans. They have been widely explored in the context of viral infection and autoimmune disease where they play key roles in protection against infection or shaping disease pathogenesis. A false dichotomy has emerged in the study of IFN-I where interferons are thought of as either beneficial or pathogenic. This 'good or bad' viewpoint excludes more nuanced interpretations of IFN-I biology - for example, it is known that IFN-I is associated with the development of systemic lupus erythematosus, yet is also protective in the context of infectious diseases and contributes to resistance to viral infection. Studies have suggested that a shared transcriptomic signature underpins both potential resistance to viral infection and susceptibility to autoimmune disease. This seems to be particularly evident in females, who exhibit increased viral resistance and increased susceptibility to autoimmune disease. The molecular mechanisms behind such a signature and the role of sex in its determination have yet to be precisely defined. From a genomic perspective, several single nucleotide polymorphisms (SNPs) in the IFN-I pathway have been associated with both infectious and autoimmune disease. While overlap between infection and autoimmunity has been described in the incidence of these SNPs, it has been overlooked in work and discussion to date. Here, we discuss the possible contributions of IFN-Is to the pathogenesis of infectious and autoimmune diseases. We comment on genetic associations between common SNPs in IFN-I or their signalling molecules that point towards roles in protection against viral infection and susceptibility to autoimmunity and propose that a shared transcriptomic and genomic immunological signature may underlie resistance to viral infection and susceptibility to autoimmunity in humans. We believe that defining shared transcriptomic and genomic immunological signatures underlying resistance to viral infection and autoimmunity in humans will reveal new therapeutic targets and improved vaccine strategies, particularly in females.

Structural Evolution of TIR-Domain Signalosomes.

TIR (Toll/interleukin-1 receptor/resistance protein) domains are cytoplasmic domains widely found in animals and plants, where they are essential components of the innate immune system. A key feature of TIR-domain function in signaling is weak and transient self-association and association with other TIR domains. An additional new role of TIR domains as catalytic enzymes has been established with the recent discovery of NAD+-nucleosidase activity by several TIR domains, mostly involved in cell-death pathways. Although self-association of TIR domains is necessary in both cases, the functional specificity of TIR domains is related in part to the nature of the TIR : TIR interactions in the respective signalosomes. Here, we review the well-studied TIR domain-containing proteins involved in eukaryotic immunity, focusing on the structures, interactions and their corresponding functional roles. Structurally, the signalosomes fall into two separate groups, the scaffold and enzyme TIR-domain assemblies, both of which feature open-ended complexes with two strands of TIR domains, but differ in the orientation of the two strands. We compare and contrast how TIR domains assemble and signal through distinct scaffolding and enzymatic roles, ultimately leading to distinct cellular innate-immunity and cell-death outcomes.

Sulfur-Induced Resistance against Pseudomonas syringae pv. actinidiae via Triggering Salicylic Acid Signaling Pathway in Kiwifruit.

Sulfur has been previously reported to modulate plant growth and exhibit significant anti-microbial activities. However, the mechanism underlying its diverse effects on plant pathogens has not been elucidated completely. The present study conducted the two-year field experiment of sulfur application to control kiwifruit canker from 2017 to 2018. For the first time, our study uncovered activation of plant disease resistance by salicylic acid after sulfur application in kiwifruit. The results indicated that when the sulfur concentration was 1.5-2.0 kg m-3, the induced effect of kiwifruit canker reached more than 70%. Meanwhile, a salicylic acid high lever was accompanied by the decline of jasmonic acid. Further analysis revealed the high expression of the defense gene, especially AcPR-1, which is a marker of the salicylic acid signaling pathway. Additionally, AcICS1, another critical gene of salicylic acid synthesis, was also highly expressed. All contributed to the synthesis of increasing salicylic acid content in kiwifruit leaves. Moreover, the first key lignin biosynthetic AcPAL gene was marked up-regulated. Thereafter, accumulation of lignin content in the kiwifruit stem and the higher deposition of lignin were visible in histochemical analysis. Moreover, the activity of the endochitinase activity of kiwifruit leaves increased significantly. We suggest that the sulfur-induced resistance against Pseudomonas syringae pv. actinidiae via salicylic activates systemic acquired resistance to enhance plant immune response in kiwifruit.