Search Results (1,367)

Plant immunity research is being reshaped by integrative multi-omics approaches that connect transcriptomic, proteomic, and interactomic data to build systems-level views of plant–pathogen interactions. This review outlines the scope and methodological landscape of these approaches, with particular emphasis on how transcriptomic and proteomic insights converge through network-based analyses to elucidate defense regulation. Transcriptomics captures infection-induced transcriptional reprogramming, while proteomics reveals protein abundance changes, post-translational modifications, and signaling dynamics essential for immune activation. Network-driven computational frameworks including iOmicsPASS, WGCNA, and DIABLO enable the identification of regulatory modules, hub genes, and concordant or discordant molecular patterns that structure plant defense responses. Interactomic techniques such as yeast two-hybrid screening and affinity purification–mass spectrometry further map host–pathogen protein–protein interactions, highlighting key immune nodes such as receptor-like kinases, R proteins, and effector-targeted complexes. Recent advances in machine learning and gene regulatory network modeling enhance the predictive interpretation of transcription–translation relationships, especially under combined or fluctuating stress conditions. By synthesizing these developments, this review clarifies how integrative multi-omics and network-based frameworks deepen understanding of the architecture and coordination of plant immune networks and support the identification of molecular targets for engineering durable pathogen resistance. Full article

Interferon-stimulated genes (ISGs) are classically recognized for their direct antiviral functions, such as viral genome degradation or replication blockade. However, emerging evidence reveals that ISGs orchestrate a broader landscape of host defense by rewiring cellular metabolism. These mechanisms are still not fully understood in the context of antiviral immunity. This review synthesizes recent advances in understanding how ISGs modulate metabolic pathways (e.g., glycolysis, lipid metabolism, amino acids, and nucleotide metabolism) to create an antiviral cellular environment. However, viruses have developed strategies to evade or counteract ISG-encoded proteins, and some even hijack certain ISGs to their advantage. Therefore, we further explore how viruses subvert these ISG-driven metabolic to evade host defenses. Overall, we summarize the current state of knowledge on the interactions between viruses and ISGs and propose that ISGs act as “protective” or “pathogenic” regulators at the dimensions of metabolism, offering new perspectives for targeting host-centered pathways to combat viral infections. Full article

Helicobacter pylori is a prevalent gastric pathogen that establishes chronic infection and contributes to gastritis, peptic ulcer disease, and gastric cancer. Its persistence depends on immune evasion strategies that promote sustained low-grade inflammation in the gastric mucosa. Nucleotide-binding oligomerization domain-like receptors (NLRs) are cytosolic pattern recognition receptors that play key roles in innate immune responses against H. pylori. Nod1 and Nod2 detect bacterial peptidoglycan delivered via the type IV secretion system or outer membrane vesicles, activating NF-κB, MAPK, and interferon signaling pathways that regulate inflammatory cytokine production, epithelial barrier function, autophagy, and antimicrobial defense. The NLRP3 inflammasome mediates the maturation of IL-1β and IL-18 primarily in myeloid cells, thereby shaping inflammatory and immunoregulatory responses during infection. In contrast, NLRC4 functions in a context-dependent manner in epithelial cells and is largely dispensable for myeloid IL-1β production. Emerging evidence also implicates noncanonical NLRs, including NLRP6, NLRP9, NLRP12, NLRX1, and NLRC5, in regulating inflammation, epithelial homeostasis, and gastric tumorigenesis. In addition, genetic polymorphisms in NLR genes influence host susceptibility to H. pylori-associated diseases. This review highlights the interplay between NLR signaling, bacterial virulence, and host immunity and identifies potential therapeutic targets. Full article

Tomato spotted wilt virus (TSWV) is one of the most important plants segmented negative-strand RNA viruses (NSVs). Plants employ the ubiquitin–proteasome system (UPS) and autophagy pathways to degrade viral effector proteins, forming a key antiviral defense layer. SnRK1 functions as a central energy sensor and plays pivotal roles in plant growth and development, as well as immune defense. However, whether SnRK1 modulates the infection of plant segmented NSVs and the underlying regulatory mechanisms remains elusive. In this study, we found that nonstructural protein NSs, a viral suppressor of RNA silencing (VSR) encoded by TSWV, specifically interacts with the catalytic α subunit of host SnRK1 (SnRK1α). NbSnRK1α promotes the degradation of NSs via the 26S proteasome pathway, independently of autophagy. Transient silencing of NbSnRK1α led to increased accumulation of the NSs protein. Furthermore, we found that NbSnRK1α significantly impairs the VSR activity of NSs by promoting its degradation, thereby restoring the host’s RNAi-mediated antiviral defense. Subsequent viral infection assays confirmed that NbSnRK1α inhibits TSWV replication, whereas silencing NbSnRK1α enhances the susceptibility of Nicotiana. benthamiana to TSWV infection and facilitates systemic viral spread and disease symptom development. Our study uncovers a new antiviral defense case by which NbSnRK1α enhances host antiviral immunity through targeting a segmented negative-strand RNA viral effector for 26S proteasomal degradation, broadening the understanding of the NbSnRK1’s role in broad-spectrum antiviral defense. Full article

Liver fibrosis induced by Schistosoma japonicum Katsurada, 1904 (S. japonicum) infection lacks effective diagnostic markers and specific anti-fibrotic therapies. Although dysregulated iron homeostasis and ferroptosis pathways may contribute to its pathogenesis, the core regulatory mechanisms remain elusive. To unravel the ferroptosis-related molecular features, this study integrated transcriptomic datasets (GSE25713 and GSE59276) from S. japonicum-infected mouse livers. Following batch effect correction and normalization, ferroptosis-related differentially expressed genes (FRDEGs) were identified. Subsequently, core hub genes were screened through the construction of a protein–protein interaction (PPI) network, functional enrichment analysis, immune infiltration evaluation, and receiver operating characteristic (ROC) analysis. The expression patterns of these hub genes were further validated in an S. japonicum-infected mouse model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study identified 7 hub genes (Lcn2, Timp1, Cth, Cp, Hmox1, Cbs, and Gclc) as key regulatory molecules. Functional enrichment analysis revealed that these hub genes are closely associated with sulfur amino acid metabolism and oxidative stress responses. Specifically, key enzymes involved in cysteine and glutathione (GSH) synthesis (Cth, Cbs, Gclc) were consistently downregulated, suggesting a severe impairment of the host antioxidant defense capacity. Conversely, pro-fibrotic and pro-inflammatory markers (Timp1, Lcn2, Hmox1) were upregulated. This molecular pattern was significantly associated with a remodeled immune microenvironment, characterized by increased infiltration of neutrophils and eosinophils. In vivo validation confirmed the expression trends of 6 hub genes, corroborating the bioinformatics predictions, while the discrepancy in Cp expression highlighted the complexity of post-transcriptional regulation in vivo. The identified hub genes demonstrated excellent diagnostic potential, with Timp1 achieving an area under the curve (AUC) of 1.000. This study elucidates the molecular link between S. japonicum infection and the ferroptosis pathway, suggesting that these hub genes may drive liver fibrosis progression by regulating sulfur metabolism and the immune microenvironment. These findings offer potential diagnostic biomarkers and novel therapeutic targets for schistosomal liver fibrosis. Full article

Plant viruses cause substantial yield and quality losses worldwide, and their rapid evolution can erode deployed host resistance. This review synthesizes current knowledge of antiviral resistance and tolerance mechanisms, using barley yellow dwarf virus (BYDV) in cereals as an illustrative case study. We first summarize key layers of plant antiviral immunity, including pre-formed physical and chemical barriers, dominant and recessive resistance genes, RNA silencing, hormone-regulated defense signaling, and degradation pathways such as the ubiquitin–proteasome system and selective autophagy. We then discuss how these mechanisms are exploited in breeding and biotechnology, covering conventional introgression, marker-assisted selection, QTL mapping and pyramiding, induced variation (mutation breeding and TILLING/ecoTILLING), transgenic strategies (pathogen-derived resistance and plantibodies), RNA interference-based approaches, and CRISPR-enabled editing of susceptibility factors. Finally, we highlight emerging nano-enabled tools and propose integrated strategies that combine genetic resistance with surveillance and vector management to improve durability under climate change and ongoing viral diversification. Full article

C-reactive protein (CRP) and serum amyloid A (SAA) are classical acute-phase proteins that exemplify humoral innate immunity, the soluble arm of the host’s first-line defense. Beyond their traditional use as biomarkers of inflammation, both proteins function as active effectors against pathogens by binding microbial components, activating complements, and modulating inflammation. However, bacteria, viruses, and fungi have co-evolved diverse mechanisms to cope with or evade these host defenses. This review aims to summarize the current understanding of CRP and SAA as soluble innate immune effectors and to highlight pathogen strategies to counteract their antimicrobial pressure. We systematically surveyed and summarized evidence from experimental and clinical studies describing “function of CRP and SAA during infection”, “CRP and SAA in innate immune defense”, and “evasion mechanisms across bacterial, viral, and fungal pathogens”. CRP and SAA are rapidly upregulated in response to infection and contribute to pathogen recognition, opsonization, and inflammation. Pathogens, however, employ multiple coping strategies, including surface modification to block CRP binding, proteolytic degradation of acute-phase proteins, shielding within biofilms, and subversion of host signaling. These countermeasures enable microbes to reduce immune clearance and promote persistence. CRP and SAA represent central elements of humoral innate immunity, shaping the outcome of host–pathogen interactions. Pathogen adaptations to these proteins illustrate an ongoing evolutionary arms race between host defense and microbial survival. A deeper understanding of these processes may open avenues for novel therapeutic approaches, such as targeting microbial evasion factors or enhancing host acute-phase responses. Full article

Rotavirus (RV) is the primary cause of severe gastroenteritis in young children, yet the long noncoding RNA (lncRNA) regulatory landscape governing the host response remains largely unmapped. To address this gap, the present study performed an integrated transcriptomic analysis of mRNA and lncRNA expression profiles in RV-infected MA104 cells at 24 h post-infection. Deep sequencing identified 11,919 high-confidence lncRNAs, revealing a massive transcriptional shift: 3651 mRNAs and 4655 lncRNAs were differentially expressed, with both populations predominantly upregulated. Functional enrichment analysis confirmed the strong activation of key innate immunity pathways, including the RIG-I-like receptor, Toll-like receptor, and TNF signaling pathways. Conversely, fundamental metabolic pathways were found to be suppressed. Crucially, the analysis of lncRNA targets highlighted their involvement in coordinating the host antiviral defense, particularly through transregulation. Experimental validation confirmed the significant upregulation of key immune-related mRNAs (OASL and C3) as well as two novel lncRNAs (lncRNA-6479 and lncRNA-4290) by qRT-PCR. The significant upregulation of OASL and C3 was validated at the protein level, confirming the biological relevance of the transcriptomic data. This study provides a foundational, genome-wide resource, identifying novel lncRNA targets for future mechanistic investigation into host–RV interactions. Full article

The nasal microbiome represents a complex and dynamic microbial ecosystem that contributes to mucosal defense, epithelial homeostasis, immune regulation, and olfactory function. Increasing evidence indicates that this microbial community actively interacts with host physiology, while alterations in its composition are associated with chronic inflammation, oxidative stress, and olfactory impairment. Such changes have been reported in conditions including chronic rhinosinusitis, allergic rhinitis, and post-viral anosmia. Beyond local effects, chronic nasal inflammation has been hypothesized to influence neuroinflammatory processes and protein aggregation pathways involving α-synuclein and tau, potentially linking nasal microbial imbalance to neurodegenerative mechanisms. However, current evidence remains largely indirect and does not support a causal relationship. This narrative review summarizes current clinical and immunological evidence on the role of the nasal microbiome in olfactory function and dysfunction, highlighting limitations of existing studies and outlining future research directions. Full article

Ectomycorrhizal (ECM) symbiosis is a fundamental mutualism crucial for forest eco-system health. Its establishment is governed by sophisticated molecular dialogue preceding physical colonization. This review synthesizes this pre-colonization crosstalk, beginning with reciprocal signal exchange where root exudates trigger fungal growth, and fungal lipochitooligosaccharides activate host symbiotic programming, often via the common symbiosis pathway. Successful colonization requires fungi to navigate plant immunity. They employ effectors, notably mycorrhiza-induced small secreted proteins (MiSSPs), to suppress defenses, e.g., by stabilizing jasmonate signaling repressors or inhibiting apoplastic proteases, establishing a localized “mycorrhiza-induced resistance.” Concurrent structural adaptations, including fungal hydrophobins, expansins, and cell wall-modifying enzymes like chitin deacetylase, facilitate adhesion and apoplastic penetration. While this sequential model integrates immune suppression with structural remodeling, current understanding is predominantly derived from a limited set of model systems. Significant knowledge gaps persist regarding species-specific determinants in non-model fungi and hosts, the influence of environmental variability and microbiome interactions, and methodological challenges in capturing early signaling in situ. This review’s main contributions are: providing a synthesized sequential model of molecular crosstalk; elucidating the dual fungal strategy of simultaneous immune suppression and structural remodeling; and identifying crucial knowledge gaps regarding non-model systems and species-specific determinants, establishing a research roadmap with implications for forest management and ecosystem sustainability. Full article

Macrophages are key innate immune cells in the host defense against pathogens. Ionizing radiation can impair macrophage functions such as phagocytosis and activate them, potentially exacerbating tissue injury. Macrophage extracellular traps (METs) are formed upon stimulation of macrophages with PAMPs or DAMPs. We hypothesized that macrophages exposed to ionizing radiation can release extracellular traps. Peritoneal macrophages were collected from C57BL/6 mice and subjected to 5 Gy radiation. We performed assays to detect METs, including the immunofluorescence of citrullination of histone H3 and cell-free DNA measurement in cell culture medium as well as cell death. The exposure of ionizing radiation killed a significant number of mouse peritoneal macrophages through pyroptosis, which was mediated by Gasdermin D (GSDMD). The onset of pyroptosis eventually caused METs by suicidal METosis via pyroptosis and vital METosis occurring in the cells surviving after exposure to radiation. We found that exposure of peritoneal macrophages to 5 Gy radiation significantly increased METosis, as revealed by increased levels of citrullinated histone H3 and an increased surface area of extracellular DNA surrounding the cells. We discovered that peptidyl arginine deiminase (PAD) 2 and 4 are required for peritoneal macrophages to generate extracellular traps in response to radiation exposure. Our data demonstrate that the ionizing radiation induces METs via the activation of GSDMD, and we confirmed the requirement of PADs for METosis after exposure to the ionizing radiation. Targeting METs may direct a new therapeutic strategy for mitigating radiation-induced tissue injury. Full article

Acinetobacter baumannii is a critical pathogen and a leading cause of hospital-acquired pneumonia, especially in immunocompromised patients. Although most research has focused on antimicrobial resistance, growing evidence shows that A. baumannii can efficiently adhere to, invade, and persist within human airway epithelial cells. Thus, the aim of this review is to summarize current knowledge on the mechanisms used by A. baumannii to establish infection, highlighting the bacterial traits responsible for attachment to airway epithelia, entry into host cells, manipulation of intracellular trafficking pathways to avoid degradation, metabolic adaptation to the host environment, and interference with immune defenses. The findings reported herein come from host–pathogen studies performed using epithelial cell lines, Galleria mellonella, and murine models, and from human primary airway cells. Despite the prominent role of the outer membrane protein OmpA, it is clear that A. baumannii pathogenicity relies on multiple, often redundant, virulence strategies to secure its intracellular niche and resist host pressures. Remarkably, strain heterogeneity in virulence traits between lab-domesticated and clinical isolates supports differential intracellular behavior and pathogenic potential. A deeper understanding of A. baumannii infection mechanisms is essential to design anti-virulence strategies that disarm this life-threatening bacterium, reduce selective pressure, limit resistance, and guide next-generation therapeutic interventions. Full article

Background/Objectives: Rotavirus remains a major cause of severe acute gastroenteritis in infants worldwide. The suboptimal efficacy of current vaccines underscores the need for alternative microbiome-based interventions, including postbiotics. Extracellular vesicles (EVs) from probiotic and commensal E. coli strains have been shown to mitigate diarrhea and enhance immune responses in a suckling-rat model of rotavirus infection. Here, we investigate the regulatory mechanisms activated by EVs in rotavirus-infected enterocytes. Methods: Polarized Caco-2 monolayers were used as a model of mature enterocytes. Cells were pre-incubated with EVs from the probiotic E. coli Nissle 1917 (EcN) or the commensal EcoR12 strain before rotavirus infection. Intracellular Ca²⁺ concentration, ROS levels, and the expression of immune- and barrier-related genes and proteins were assessed at multiple time points post-infection. Results: EVs from both strains exerted broad protective effects against rotavirus-induced cellular dysregulation, with several responses being strain-specific. EVs interfered with viral replication by counteracting host cellular processes essential for rotavirus propagation. Specifically, EV treatment significantly reduced rotavirus-induced intracellular Ca²⁺ mobilization, ROS production, and COX-2 expression. In addition, both EV types reduced virus-induced mucin secretion and preserved tight junction organization, thereby limiting viral access to basolateral coreceptors. Additionally, EVs enhanced innate antiviral defenses via distinct, strain-dependent pathways: EcN EVs amplified IL-8-mediated responses, whereas EcoR12 EVs preserved the expression of interferon-related signaling genes. Conclusions: EVs from EcN and EcoR12 act through multiple complementary mechanisms to restrict rotavirus replication, spread, and immune evasion. These findings support their potential as effective postbiotic candidates for preventing or treating rotavirus infection. Full article

Maize (Zea mays L.) is a major economic crop highly susceptible to Colletotrichum graminicola, the causal agent of anthracnose leaf blight, which causes substantial annual yield losses. This fungal pathogen employs numerous effectors to manipulate plant immunity, yet the functions of many secreted proteins during biphasic infection remain poorly characterized. In this study, we identified CgMas2, a candidate secreted protein in C. graminicola and a homolog of Magnaporthe oryzae MoMas2. Deletion of CgMAS2 in the wild-type strain CgM2 did not affect fungal vegetative growth or conidial morphology but significantly impaired virulence on maize leaves. Leaf sheath infection assays revealed that CgMas2 is required for biotrophic invasive hyphal growth, as the mutant showed defective spreading of invasive hyphae to adjacent cells. Subcellular localization analysis indicated that CgMas2 localizes to the cytoplasm of conidia and to the primary infection hyphae. Furthermore, DAB staining demonstrated that disrupt of CgMAS2 leads to host reactive oxygen species (ROS) accumulation. Comparative transcriptome analysis of maize infected with ΔCgmas2 versus CgM2 revealed enrichment of GO terms related to peroxisome and defense response, along with up-regulation of benzoxazinoid biosynthesis genes (benzoxazinone biosynthesis 3, 4 and 5) at 60 h post-inoculation (hpi). Conversely, six ethylene-responsive transcription factors (ERF2, ERF3, ERF56, ERF112, ERF115 and ERF118) involved in ethylene signaling pathways were down-regulated at 96 hpi. These expression patterns were validated by RT-qPCR. Collectively, our results demonstrate that CgMas2 not only promotes invasive hyphal growth during the biotrophic stage but may also modulate phytohormone signaling and defense compound biosynthesis during the necrotrophic phase of infection. Full article

Signal transducer and activator of transcription 2 (STAT2) is a key component of the type I interferon (IFN-I/III) signaling pathway, which is pivotal in host defense against cancer and viral infections and in shaping immune responses. Building on our previously reported conditional Stat2 knockout (KO) mouse, we expand its utility by validating additional tissue-specific models and exploring novel functional contexts. Mice carrying loxP-flanked Stat2 alleles were crossed with CMV-Cre, Cdx2-Cre or CD11c-Cre mice. Deletion of STAT2 was validated by PCR genotyping and western blotting in the relevant tissues. To confirm defective IFN-I signaling with STAT2 deletion, IFN-β stimulation of splenocytes from CMV-Cre Stat2 KO mice showed a lack of induction of canonical IFN-I target genes, confirming functional disruption of the pathway. In vivo, global Stat2 deletion significantly impaired the antitumor efficacy of IFN-β treatment. Similarly, lung fibroblasts isolated from globally deleted Stat2 KO mice showed defective antiviral responses to IFN-β. Tissue-specific Cre models demonstrated selective ablation of STAT2 in target compartments without affecting its expression in non-target tissues. Together, these studies expand our published conditional Stat2 KO findings and highlight the value of this model as a versatile platform for dissecting STAT2-dependent signaling pathways in a tissue- and disease-specific manner. Full article