Host Defense Responses Research Articles

Potential effects of shift work on skin autoimmune diseases.

Shift work is associated with systemic chronic inflammation, impaired host and tumor defense and dysregulated immune responses to harmless antigens such as allergens or auto-antigens. Thus, shift workers are at higher risk to develop a systemic autoimmune disease and circadian disruption with sleep impairment seem to be the key underlying mechanisms. Presumably, disturbances of the sleep-wake cycle also drive skin-specific autoimmune diseases, but epidemiological and experimental evidence so far is scarce. This review summarizes the effects of shift work, circadian misalignment, poor sleep, and the effect of potential hormonal mediators such as stress mediators or melatonin on skin barrier functions and on innate and adaptive skin immunity. Human studies as well as animal models were considered. We will also address advantages and potential pitfalls in animal models of shift work, and possible confounders that could drive skin autoimmune diseases in shift workers such as adverse lifestyle habits and psychosocial influences. Finally, we will outline feasible countermeasures that may reduce the risk of systemic and skin autoimmunity in shift workers, as well as treatment options and highlight outstanding questions that should be addressed in future studies.

The lymphatic endothelium-derived follistatin: activin A axis regulates neutrophil motility in response to Pseudomonas aeruginosa.

The lymphatic system plays an active role during infection, however the role of lymphatic-neutrophil interactions in host-defense responses is not well understood. During infection with pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus and Yersinia pestis, neutrophils traffic from sites of infection through the lymphatic vasculature, to draining lymph nodes to interact with resident lymphocytes. This process is poorly understood, in part, due to the lack of in vitro models of the lymphatic system. Here we use a 3D microscale lymphatic vessel model to examine neutrophil-lymphatic cell interactions during host defense responses to pathogens. In previous work, we have shown that follistatin is secreted at high concentrations by lymphatic endothelial cells during inflammation. Follistatin inhibits activin A, a member of the TGF-β superfamily, and, together, these molecules form a signaling pathway that plays a role in regulating both innate and adaptive immune responses. Although follistatin and activin A are constitutively produced in the pituitary, gonads and skin, their major source in the serum and their effects on neutrophils are poorly understood. Here we report a microfluidic model that includes both blood and lymphatic endothelial vessels, and neutrophils to investigate neutrophil-lymphatic trafficking during infection with P. aeruginosa. We found that lymphatic endothelial cells produce secreted factors that increase neutrophil migration toward P. aeruginosa, and are a significant source of both follistatin and activin A during Pseudomonas infection. We determined that follistatin produced by lymphatic endothelial cells inhibits activin A, resulting in increased neutrophil migration. These data suggest that the follistatin:activin A ratio influences neutrophil trafficking during infection with higher ratios increasing neutrophil migration.

Two nucleotide sugar transporters are important for cell wall integrity and full virulence of Magnaporthe oryzae.

Cell wall polysaccharides play key roles in fungal development, virulence, and resistance to the plant immune system, and are synthesized from many nucleotide sugars in the endoplasmic reticulum (ER)-Golgi secretory system. Nucleotide sugar transporters (NSTs) are responsible for transporting cytosolic-derived nucleotide sugars to the ER lumen for processing, but their roles in plant-pathogenic fungi remain to be revealed. Here, we identified two important NSTs, NST1 and NST2, in the rice blast fungus Magnaporthe oryzae. Both NSTs were localized in the ER, which was consistent with a function in transporting nucleotide sugar for processing in the ER. Sugar transport property analysis suggested that NST1 is involved in transportation of mannose and glucose, while NST2 is only responsible for mannose transportation. Accordingly, deletion ofNSTs resulted in a significant decrease in corresponding soluble saccharides abundance and defect in sugar utilization. Moreover, bothNSTs played important roles in cell wall integrity, were involved in asexual development, and were required for full virulence. The NST mutants exhibited decreasing external glycoproteins and exposure of inner chitin, which resulted in activation of the host defence response. Altogether, our results revealed that two sugar transporters are required for fungal cell wall polysaccharides accumulation and full virulence of M.oryzae.

Comparisons of coagulation characteristics between elderly and non-elderly patients with sepsis: A prospective study

BackgroundA blunt host defense response in older patients may contribute to different coagulation responses during sepsis. We aimed to investigate the differences in coagulation parameters between elderly and non-elderly patients with sepsis. MethodsAdult patients diagnosed with sepsis within 24 hours after admission to the intensive care unit between September 2018 and December 2020 were prospectively enrolled. Patients were categorized into the adult (18–64 years) and elderly (age ≥65 years) groups. Conventional coagulation parameters and inflammatory markers were measured on intensive care unit admission and on Days 3 and 7. Thromboelastography was performed on intensive care unit admission. The differences in the coagulation parameters between the 2 groups were evaluated. The adult and elderly patients were matched to adjust for baseline characteristics. Correlations between inflammatory markers and coagulation-related parameters were also analyzed. ResultsOf the 567 patients, 303 (53.4%) were elderly. Compared with adult patients, elderly patients had lower prothrombin time elevation, lower fibrinogen, D-dimer, and fibrin/Fib degradation product levels, and lower proportion of disseminated intravascular coagulation on intensive care unit admission; and, they had lower dynamic platelet, lower fibrinogen, and D-dimer levels during the first week in the intensive care unit. Thromboelastography parameters were generally within the normal range, although elderly patients had lower R and K values and a higher alpha angle. Comparisons of coagulation parameters between the 2 groups revealed similar results in the matched cohort. The inflammatory markers correlated with prothrombin time, activated partial thromboplastin time, and antithrombin III. ConclusionElderly patients had milder coagulation activation, accompanied by a decreased inflammatory response during sepsis, compared to non-elderly patients.

Pyridoxine biosynthesis protein MoPdx1 affects the development and pathogenicity of Magnaporthe oryzae.

B vitamins are essential micro-organic compounds for the development of humans and animals. Vitamin B6 comprises a group of components including pyridoxine, pyridoxal, and pyridoxamine. In addition, vitamin B6 acts as the coenzymes in amino acid biosynthesis, decarboxylation, racemic reactions, and other biological processes. In this study, we found that the expressions of a gene encoding pyridoxine biosynthesis protein (PDX1) were significantly upregulated in the early infectious stages in M. oryzae. Furthermore, deletion of MoPDX1 slowed vegetative growth on different media, especially on MM media, and the growth defect was rescued when MoPdx1-protein was expressed in mutants strains and when commercial VB6 (pyridoxine) was added exogenously. However, VB6 content in different strains cultured in CM media has no significant difference, suggested that MoPdx1 was involved in de novo VB6 biosynthesis not in uptake process, and VB6 regulates the vegetative growth of M. oryzae. The ΔMopdx1 mutants presented abnormal appressorium turgor, slowed invasive growth and reduced virulence on rice seedlings and sheath cells. MoPdx1 was located in the cytoplasm and present in spore and germ tubes at 14 hours post inoculation (hpi) and then transferred into the appressorium at 24 hpi. Addition of VB6 in the conidial suspentions could rescue the defects of appressorium turgor pressure at 14 hpi or 24 hpi, invasive growth and pathogenicity of the MoPDX1 deletion mutants. Indicated that MoPdx1 affected the appressorium turgor pressure, invasive growth and virulence mainly depended on de novo VB6, and VB6 was biosynthesized in conidia, then transported into the appressorium, which play important roles in substances transportation from conidia to appressorium thus to regulate the appressorium turgor pressure. However, deletion of MoPDX1 did not affect the ability that scavenge ROS produced by rice cells, and the mutant strains were unable to activate host defense responses. In addition, co-immunoprecipitation (Co-IP) assays investigating potential MoPdx1-interacting proteins suggested that MoPdx1 might take part in multiple pathways, especially in the ribosome and in biosynthesis of some substances. These results indicate that vitamins are involved in the development and pathogenicity of M. oryzae.

Multi-Tissue Transcriptome Study of Innate Immune Gene Expression Profiling Reveals Negative Energy Balance Altered the Defense and Promoted System Inflammation of Dairy Cows.

Negative energy balance (NEB) during the perinatal period leads to metabolic and immunological disorders in dairy cows, resulting in systemic responses and inflammation. The innate immune system is crucial for the host's protection and inflammatory response. However, systematic research is still lacking on how NEB affects the innate immune system to alter the 'host defense capability and inflammatory response. In this investigation, raw transcriptome data of adipose, blood, endometrial, hypothalamus, and liver tissues were downloaded from a public database, cleaned, aligned, quantified, and batch-corrected. The innate immune gene list was retrieved from innateDB, followed by the expression matrix of innate immune genes in various tissues for differential expression analysis, principle component analysis (PCA), and gene set enrichment analysis (GSEA). Under the effect of NEB, adipose tissue had the most differentially expressed genes, which were predominantly up-regulated, whereas blood GSEA had the most enriched biological processes, which were predominantly down-regulated. The gene sets shared by different tissues, which are predominantly involved in biological processes associated with defense responses and inflammation, were dramatically down-regulated in endometrial tissues and highly up-regulated in other tissues. Under the impact of NEB, LBP, PTX3, S100A12, and LCN2 play essential roles in metabolism and immunological control. In conclusion, NEB can downregulate the defensive response of innate immune genes in endometrial, upregulate the immune and inflammatory response of other tissues, activate the host defense response, and increase the systemic inflammatory response. The analysis of the effects of NEB on innate immune genes from the multiple tissues analysis provides new insights into the crosstalk between metabolism and immunity and also provides potential molecular targets for disease diagnosis and disease resistance breeding in dairy cows.

Involvement of the E3 ubiquitin ligase Cblb in host defense and evaluation of transcriptome during Trueperella pyogenes infection

Trueperella pyogenes (T. pyogenes) is a versatile and ingenious bacterium that causes severe suppurative injuries in lots of economically important ruminants. The underlying pathogenesis of T. pyogenes infection remains poorly understood. In the current study, we performed transcriptome sequencing of mouse blood tissue infected with T. pyogenes. A total of 36.73 G clean data were collected, and 136 differentially expressed genes were obtained in the infection group compared to the control group. In addition, we found that the E3 ubiquitin ligase Cblb exhibited significant upregulation in the infection groups compared to the control group. Mechanistically, T. pyogenes infection markedly enhanced the expression of Cblb and regulated the host defense response. Inhibiting Cblb expression with Cblb siRNA impaired the inflammatory response and reduced the effect of phagocytosis in RAW264.7 murine macrophages. Intriguingly, overexpression of Cblb induced a strong inflammatory response and enhanced phagocytosis against T. pyogenes infection in macrophages. More importantly, the overexpression of Cblb significantly reduced the bacterial load and protected mice from the T. pyogenes infections. Therefore, our findings reveal that Cblb is a novel and potential regulator in response to T. pyogenes infection and shed new light on the development of promising treatments against T. pyogenes-related diseases.

Tyrosine kinase inhibitors can activate the NLRP3 inflammasome in myeloid cells through lysosomal damage and cell lysis.

Inflammasomes are intracellular protein complexes that promote an inflammatory host defense in response to pathogens and damaged or neoplastic tissues and are implicated in inflammatory disorders and therapeutic-induced toxicity. We investigated the mechanisms of activation for inflammasomes nucleated by NOD-like receptor (NLR) protiens. A screen of a small-molecule library revealed that several tyrosine kinase inhibitors (TKIs)-including those that are clinically approved (such as imatinib and crizotinib) or are in clinical trials (such as masitinib)-activated the NLRP3 inflammasome. Furthermore, imatinib and masitinib caused lysosomal swelling and damage independently of their kinase target, leading to cathepsin-mediated destabilization of myeloid cell membranes and, ultimately, cell lysis that was accompanied by potassium (K+) efflux, which activated NLRP3. This effect was specific to primary myeloid cells (such as peripheral blood mononuclear cells and mouse bone marrow-derived dendritic cells) and did not occur in other primary cell types or various cell lines. TKI-induced lytic cell death and NLRP3 activation, but not lysosomal damage, were prevented by stabilizing cell membranes. Our findings reveal a potential immunological off-target of some TKIs that may contribute to their clinical efficacy or to their adverse effects.

Revisiting the sialome of the cat flea Ctenocephalides felis.

The hematophagous behaviour emerged independently in several instances during arthropod evolution. Survey of salivary gland and saliva composition and its pharmacological activity led to the conclusion that blood-feeding arthropods evolved a distinct salivary mixture that can interfere with host defensive response, thus facilitating blood acquisition and pathogen transmission. The cat flea, Ctenocephalides felis, is the major vector of several pathogens, including Rickettsia typhi, Rickettsia felis and Bartonella spp. and therefore, represents an important insect species from the medical and veterinary perspectives. Previously, a Sanger-based sialome of adult C. felis female salivary glands was published and reported 1,840 expressing sequence tags (ESTs) which were assembled into 896 contigs. Here, we provide a deeper insight into C. felis salivary gland composition using an Illumina-based sequencing approach. In the current dataset, we report 8,892 coding sequences (CDS) classified into 27 functional classes, which were assembled from 42,754,615 reads. Moreover, we paired our RNAseq data with a mass spectrometry analysis using the translated transcripts as a reference, confirming the presence of several putative secreted protein families in the cat flea salivary gland homogenates. Both transcriptomic and proteomic approaches confirmed that FS-H-like proteins and acid phosphatases lacking their putative catalytic residues are the two most abundant salivary proteins families of C. felis and are potentially related to blood acquisition. We also report several novel sequences similar to apyrases, odorant binding proteins, antigen 5, cholinesterases, proteases, and proteases inhibitors, in addition to putative novel sequences that presented low or no sequence identity to previously deposited sequences. Together, the data represents an extended reference for the identification and characterization of the pharmacological activity present in C. felis salivary glands.

Wheat leaf rust fungus effector Pt13024 is avirulent to TcLr30.

Wheat leaf rust, caused by Puccinia triticina Eriks. (Pt), is a global wheat disease threatening wheat production. Dissecting how Pt effector proteins interact with wheat has great significance in understanding the pathogenicity mechanisms of Pt. In the study, the cDNA of Pt 13-5-72 interacting with susceptible cultivar Thatcher was used as template to amplify Pt13024 gene. The expression pattern and structure of Pt13024 were analyzed by qRT-PCR and online softwares. The secretion function of Pt13024 signal peptide was verified by the yeast system. Subcellular localization of Pt13024 was analyzed using transient expression on Nicotiana benthamiana. The verification that Pt13024 inhibited programmed cell death (PCD) was conducted on N. benthamiana and wheat. The deletion mutation of Pt13024 was used to identify the virulence function motif. The transient transformation of wheat mediated by the type III secretion system (TTSS) was used to analyze the activity of regulating the host defense response of Pt13024. Pt13024 gene silencing was performed by host-induced gene silencing (HIGS). The results showed that Pt13024 was identified as an effector and localized in the cytoplasm and nucleus on the N. benthamiana. It can inhibit PCD induced by the Bcl-2-associated X protein (BAX) from mice and infestans 1 (INF1) from Phytophthora infestans on N. benthamiana, and it can also inhibit PCD induced by DC3000 on wheat. The amino acids 22 to 41 at N-terminal of the Pt13024 are essential for the inhibition of programmed cell death (PCD) induced by BAX. The accumulation of reactive oxygen species and deposition of callose in near-isogenic line TcLr30, which is in Thatcher background with Lr30, induced by Pt13024 was higher than that in 41 wheat leaf rust-resistant near-isogenic lines (monogenic lines) with different resistance genes and Thatcher. Silencing of Pt13024 reduced the leaf rust resistance of Lr30 during the interaction between Pt and TcLr30. We can conclude that Pt13024 is avirulent to TcLr30 when Pt interacts with TcLr30. These findings lay the foundation for further investigations into the role of Pt effector proteins in pathogenesis and their regulatory mechanisms.

Pathophysiology of Inflammatory Bowel Disease: Innate Immune System.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a heterogeneous state of chronic intestinal inflammation with no exact known cause. Intestinal innate immunity is enacted by neutrophils, monocytes, macrophages, and dendritic cells (DCs), and innate lymphoid cells and NK cells, characterized by their capacity to produce a rapid and nonspecific reaction as a first-line response. Innate immune cells (IIC) defend against pathogens and excessive entry of intestinal microorganisms, while preserving immune tolerance to resident intestinal microbiota. Changes to this equilibrium are linked to intestinal inflammation in the gut and IBD. IICs mediate host defense responses, inflammation, and tissue healing by producing cytokines and chemokines, activating the complement cascade and phagocytosis, or presenting antigens to activate the adaptive immune response. IICs exert important functions that promote or ameliorate the cellular and molecular mechanisms that underlie and sustain IBD. A comprehensive understanding of the mechanisms underlying these clinical manifestations will be important for developing therapies targeting the innate immune system in IBD patients. This review examines the complex roles of and interactions among IICs, and their interactions with other immune and non-immune cells in homeostasis and pathological conditions.

Natural variation in Avr3D1 from Zymoseptoria sp. contributes to quantitative gene-for-gene resistance and to host specificity.

Successful host colonization by plant pathogens requires the circumvention of host defense responses, frequently through sequence modifications in secreted pathogen proteins known as avirulence factors (Avrs). Although Avr sequences are often polymorphic, the contribution of these polymorphisms to virulence diversity in natural pathogen populations remains largely unexplored. We used molecular genetic tools to determine how natural sequence polymorphisms of the avirulence factor Avr3D1 in the wheat pathogen Zymoseptoria tritici contributed to adaptive changes in virulence. We showed that there is a continuous distribution in the magnitude of resistance triggered by different Avr3D1 isoforms and demonstrated that natural variation in an Avr gene can lead to a quantitative resistance phenotype. We further showed that homologues of Avr3D1 in two nonpathogenic sister species of Z.tritici are recognized by some wheat cultivars, suggesting that Avr-R gene-for-gene interactions can contribute to nonhost resistance. We suggest that the mechanisms underlying host range, qualitative resistance, and quantitative resistance are not exclusive.

Apoptosis Inhibitor of Macrophages Contributes to the Chronicity of Mycobacterium avium Infection by Promoting Foamy Macrophage Formation

In Mycobacterium avium infections, macrophages play a critical role in the host defense response. Apoptosis inhibitor of macrophage (AIM), also known as CD5L, may represent a novel supportive therapy against various diseases, including metabolic syndrome and infectious diseases. The mechanisms of AIM include modulating lipid metabolism in macrophages and other host cells. We investigated the role of AIM in M. avium infections in vitro and in vivo. In a mouse model of M. avium pneumonia, foamy macrophages were induced 6 wk after infection. The bacteria localized in these macrophages. Flow cytometric analysis also confirmed that the percentage of CD11chighMHCclassIIhigh interstitial and alveolar macrophages, a cell surface marker defined as foamy macrophages, increased significantly after infection. AIM in alveolar lavage fluid and serum gradually increased after infection. Administration of recombinant AIM significantly increased the number of bacteria in the lungs of mice, accompanied by the induction of inflammatory cytokine and iNOS expression. In mouse bone marrow-derived macrophages, the mRNA expression of AIM after M. avium infection and the amount of AIM in the supernatant increased prior to the increase in intracellular bacteria. Infected cells treated with anti-AIM Abs had fewer bacteria and a higher percentage of apoptosis-positive cells than infected cells treated with isotype control Abs. Finally, AIM in the sera of patients with M. avium-pulmonary disease was measured and was significantly higher than in healthy volunteers. This suggests that AIM production is enhanced in M. avium-infected macrophages, increasing macrophage resistance to apoptosis and providing a possible site for bacterial growth.

Impact of resveratrol and zinc on biomarkers of oxidative stress induced by Trichinella spiralis infection.

Trichinellosis is a re-emerging worldwide foodborne zoonosis. Oxidative stress is one of the most common detrimental effects caused by trichinellosis. In addition, Trichinella infection poses an infinite and major challenge to the host's immune system. Resistance and side effects limit the efficiency of the existing anti-trichinella medication. Given that concern, this work aimed to investigate the anti-helminthic, antioxidant, anti-inflammatory and immunomodulatory effects of resveratrol and zinc during both phases of Trichinella spiralis infection. Sixty-four Swiss albino mice were divided into four equal groups: non-infected control, infected control, infected and treated with resveratrol, and infected and treated with zinc. Animals were sacrificed on the 7th and 35th days post-infection for intestinal and muscular phase assessments. Drug efficacy was assessed by biochemical, parasitological, histopathological, immunological, and immunohistochemical assays. Resveratrol and zinc can be promising antiparasitic, antioxidant, anti-inflammatory, and immunomodulatory agents, as evidenced by the significant decrease in parasite burden, the significant improvement of liver and kidney function parameters, the increase in total antioxidant capacity (TAC), the reduction of malondialdehyde (MDA) level, the increase in nuclear factor (erythroid-derived 2)-like-2 factor expression, and the improvement in histopathological findings. Moreover, both drugs enhanced the immune system and restored the disturbed immune balance by increasing the interleukin 12 (IL-12) level. In conclusion, resveratrol and zinc provide protection for the host against oxidative harm and the detrimental effects produced by the host's defense response during Trichinella spiralis infection, making them promising natural alternatives for the treatment of trichinellosis.

Proteomic Profiling of Host Response in the Cereal Crop Triticum aestivum to the Mycotoxin, 15-Acetyldeoxynivalenol, Produced by the Fungal Pathogen, Fusarium graminearum.

Deoxynivalenol (DON) is a destructive mycotoxin produced by the fungal pathogen Fusarium graminearum in the devastating cereal disease Fusarium head blight (FHB). Host resistance to FHB has been identified within some of these crops (e.g., wheat, barley, corn); however, identification of how the host reduces the production of, and tolerates, DON to lessen the effects of the disease still requires further discovery. The field of quantitative proteomics is an effective tool for measuring and quantifying host defense responses to external factors, including the presence of pathogens and toxins. Success within this area of research has increased through recent technological developments (e.g., instrument sensitivity) and the accessibility of data analysis programs. One advancement we leverage is the ability to label peptides with isobaric mass tags to allow for sample multiplexing, reducing mass spectrometer run times, and providing accurate quantification. In this protocol, we exemplify this methodology to identify protein-level responses to DON within both FHB-resistant and FHB-susceptible Triticum aestivum cultivars using tandem mass tags for quantitative labeling combined with liquid-chromatography-MS/MS (LC-MS/MS) analysis. Furthermore, this protocol can be extrapolated for the identification of host responses under various conditions, including infection and environmental fluctuations, to elucidate changes in proteomic profiling in diverse biological contexts.

Hypoxia Attenuates Colonic Innate Immune Response and Inhibits TLR4/NF-κB Signaling Pathway in Lipopolysaccharide-Induced Colonic Epithelial Injury Mice.

High altitude hypoxia can lead to a spectrum of gastrointestinal problems. As the first line of host immune defense, innate immune response in the intestinal mucosa plays a pivotal role in maintaining intestinal homeostasis and protecting against intestinal injury at high altitude. This study aimed to investigate the effect of hypoxia on the colonic mucosal barrier and toll-like receptor 4 (TLR4)-mediated innate immune responses in the colon. The mice were exposed to a hypobaric chamber to simulate a 5,000 m plateau environment for 7 days, and the colonic mucosa changes were recorded. At the same time, the inflammation model was established by lipopolysaccharide (LPS) to explore the effects of hypoxia on the TLR4/nuclear factor kappa B (NF-κB) signaling pathway and its downstream inflammatory factors [tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ] in the colon. We found that hypoxic exposure caused weight loss and structural disturbance of the colonic mucosa in mice. Compared with the control group, the protein levels of TLR4 [fold change (FC) = 0.75 versus FC = 0.23], MyD88 (FC = 0.80 versus FC = 0.30), TIR-domain-containing adaptor protein inducing interferon-β (TRIF: FC = 0.89 versus FC = 0.38), and NF-κB p65 (FC = 0.75 versus FC = 0.24) in the colon of mice in the hypobaric hypoxia group were significantly decreased. LPS-induced upregulation of the TLR4/NF-κB signaling and its downstream inflammatory factors was inhibited by hypoxia. Specifically, compared with the LPS group, the protein levels of TLR4 (FC = 1.18, FC = 0.86), MyD88 (FC = 1.20, FC = 0.80), TRIF (FC = 1.20, FC = 0.86), and NF-κB p65 (FC = 1.29, FC = 0.62) and the mRNA levels of IL-1β (FC = 7.38, FC = 5.06), IL-6 (FC = 16.06, FC = 9.22), and IFN-γ (FC = 2.01, FC = 1.16) were reduced in the hypobaric hypoxia plus LPS group. Our findings imply that hypoxia could lead to marked damage of the colonic mucosa and a reduction of TLR4-mediated colonic innate immune responses, potentially reducing host defense responses to colonic pathogens.

The Puccinia striiformis effector Hasp98 facilitates pathogenicity by blocking the kinase activity of wheat TaMAPK4.

The obligate biotrophic fungus Puccinia striiformis f. sp. tritici (Pst) employs virulence effectors to disturb host immunity and causes devastating stripe rust disease. However, our understanding of how Pst effectors regulate host defense responses remains limited. In this study, we determined that the Pst effector Hasp98, which is highly expressed in Pst haustoria, inhibits plant immune responses triggered by flg22 or nonpathogenic bacteria. Overexpression of Hasp98 in wheat (Triticum aestivum) suppressed avirulent Pst-triggered immunity, leading to decreased H2 O2 accumulation and promoting P. striiformis infection, whereas stable silencing of Hasp98 impaired P. striiformis pathogenicity. Hasp98 interacts with the wheat mitogen-activated protein kinase TaMAPK4, a positive regulator of plant resistance to stripe rust. The conserved TEY motif of TaMAPK4 is important for its kinase activity, which is required for the resistance function. We demonstrate that Hasp98 inhibits the kinase activity of TaMAPK4 and that the stable silencing of TaMAPK4 compromises wheat resistance against P. striiformis. These results suggest that Hasp98 acts as a virulence effector to interfere with the MAPK signaling pathway in wheat, thereby promoting P. striiformis infection.

Emerging Role of Neutrophil Extracellular Traps in Gastrointestinal Tumors: A Narrative Review

Neutrophil extracellular traps (NETs) are extracellular fibrous networks consisting of depolymerized chromatin DNA skeletons with a variety of antimicrobial proteins. They are secreted by activated neutrophils and play key roles in host defense and immune responses. Gastrointestinal (GI) malignancies are globally known for their high mortality and morbidity. Increasing research suggests that NETs contribute to the progression and metastasis of digestive tract tumors, among them gastric, colon, liver, and pancreatic cancers. This article explores the formation of NETs and reviews the role that NETs play in the gastrointestinal oncologic microenvironment, tumor proliferation and metastasis, tumor-related thrombosis, and surgical stress. At the same time, we analyze the qualitative and quantitative detection methods of NETs in recent years and found that NETs are specific markers of coronavirus disease 2019 (COVID-19). Then, we explore the possibility of NET inhibitors for the treatment of digestive tract tumor diseases to provide a new, efficient, and safe solution for the future therapy of gastrointestinal tumors.

In Vitro and In Planta Antagonistic Effect of Endophytic Bacteria on Blight Causing Xanthomonas axonopodis pv. punicae: A Destructive Pathogen of Pomegranate

Pomegranate bacterial blight caused by Xanthomonas axonopodis pv. punicae (Xap) is a highly destructive disease. In the absence of host resistance to the disease, we aimed to evaluate the biocontrol potential of endophytic bacteria against Xap. Thus, in this study, we isolated endophytes from pomegranate plants, identified them on the basis of 16S rDNA sequencing, tested them against Xap, and estimated the endophyte-mediated host defense response. The population of isolated endophytes ranged from 3 × 106 to 8 × 107 CFU/g tissue. Furthermore, 26 isolates were evaluated for their biocontrol activity against Xap, and all the tested isolates significantly reduced the in vitro growth of Xap (15.65% ± 1.25% to 56.35% ± 2.66%) as compared to control. These isolates could reduce fuscan, an uncharacterized factor of Xap involved in its aggressiveness. Lower blight incidence (11.6%) and severity (6.1%) were recorded in plants sprayed with endophytes 8 days ahead of Xap spray (Set-III) as compared to control plants which were not exposed to endophytes (77.33 and 50%, respectively%) during in vivo evaluation. Moreover, significantly high phenolic and chlorophyll contents were estimated in endophyte-treated plants as compared to control. The promising isolates mostly belonged to the genera Bacillus, Burkholderia, and Lysinibacillus, and they were deposited to the National Agriculturally Important Microbial Culture Collection, India.

Degradation of HDAC10 by autophagy promotes IRF3-mediated antiviral innate immune responses.

Histone deacetylases (HDACs) play important roles in immunity and inflammation. Through functional screening, we identified HDAC10 as an inhibitor of the type I interferon (IFN) response mediated by interferon regulatory factor 3 (IRF3). HDAC10 abundance was decreased in mouse macrophages in response to innate immune stimuli and was reduced in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) compared with that in PBMCs from healthy donors. Deficiency in HDAC10 in mouse embryonic fibroblasts and in mice promoted the expression of genes encoding type I IFNs and of IFN-stimulated genes (ISGs), leading to enhanced antiviral responses in vitro and in vivo. HDAC10 bound in a deacetylase-independent manner to IRF3 in uninfected cells to inhibit the phosphorylation of IRF3 at Ser396 by TANK-binding kinase 1 (TBK1). Upon viral infection, HDAC10 was targeted for autophagy-mediated degradation through its interaction with LC3-II. Consequently, IRF3 phosphorylation was increased, which resulted in enhanced type I IFN production and antiviral responses. Our findings identify a potential target for improving host defense responses against pathogen infection and for treating autoimmune disease.