Search Results (355)

Transmissible gastroenteritis (TGE), caused by the TGE virus (TGEV), is a highly contagious enteric disease characterized by vomiting, dehydration, and watery diarrhea. It mainly endangers piglets within two weeks of age, with a 100% mortality rate, inflicting severe economic losses on the global swine industry. Since enteric tropism of the virus and mucosa serves as the first line of defense against viral invasion, an oral vaccine inducing sufficient secretory immunoglobulin A (SIgA) antibodies in animals should be developed. Being a generally recognized as safe (GRAS) microorganism, Bacillus subtilis can form endospores under extreme environmental conditions, which confer resistance to the hostile gastric environment and have been widely employed as delivery vehicles for oral vaccines owing to their immunoadjuvant activity and non-specific antidiarrheal effects. In this study, the AD antigenic epitope of the TGEV S protein was selected as the immunogen. The mature peptide of the B subunit of the heat-labile enterotoxin from enterotoxigenic Escherichia coli served as a mucosal adjuvant, and B. subtilis WB800N was used as the delivery host to construct the recombinant strain pHT43-LTB-AD/WB800N. After confirming the successful expression of the target protein, oral immunization was performed using mice as a model. The results demonstrated that this recombinant strain induced robust mucosal, humoral, and cellular immunity, along with considerable levels of neutralizing antibodies. These findings indicate that recombinant B. subtilis could serve as an oral vaccine candidate to combat TGEV infections. Full article

ROS derived from NADPH oxidase, particularly NOX2, are central to antimicrobial defense, coupling direct pathogen killing with redox signaling that shapes inflammation. This narrative review integrates recent advances on NOX2 structure, assembly, and spatiotemporal control in phagocytes, and outlines how ROS interact with NF-κB, MAPK, and Nrf2 networks to coordinate microbicidal activity and immune modulation. We summarize evidence that both ROS deficiency, as in chronic granulomatous disease, and uncontrolled excess, as in sepsis and severe COVID-19, drive clinically significant pathology, emphasizing the need for precise redox balance. Emerging therapeutic strategies include selective NOX2 inhibitors that limit pathological oxidative bursts, redox-modulating peptides that disrupt upstream activation cues, and Nrf2 activators that enhance endogenous antioxidant capacity, with attention to dosing challenges that preserve host defense while mitigating tissue injury. Key gaps remain in biomarker standardization, real-time in vivo ROS monitoring, and translation from animal models to patients, motivating personalized, combination approaches to redox medicine in infectious diseases. Full article

Extraintestinal pathogenic Escherichia coli (ExPEC) is a major cause of infections of the urinary tract, the bloodstream, and other non-intestinal sites in humans. ExPEC often resists the bactericidal action of human immune defenses including complement, antimicrobial peptides, antibodies, and cell-mediated killing. This review provides an overview of the main host defense strategies, and the mechanisms and molecules ExPEC engages to resist these human immune responses. Surface-exposed polysaccharides, outer membrane proteins, cytotoxins, and proteases are all part of the bacterial arsenal of defenses that can neutralize many of the host’s immune defenses. These factors work in concert to enable ExPEC to survive and thrive in extraintestinal environments of the human body. Full article

Peptidoglycan recognition proteins (PGRPs) are conserved pattern recognition receptors (PRRs) that play key roles in insect innate immunity by binding bacterial peptidoglycan (PGN) and activating downstream signaling pathways. The Dendrolimus kikuchii, a major defoliator of coniferous forests in southern China, has incompletely characterized immune defenses. This study systematically identified the PGRP gene family in D. kikuchii based on genome-wide data, identifying 10 PGRP genes with typical PGRP/Amidase_2 conserved domains, including 6 PGRP-S proteins and 4 PGRP-L proteins. Additionally, to further investigate the evolutionary relationships of these PGRP genes, a maximum likelihood (ML) phylogenetic tree was constructed using PGRP amino acid sequences from 6 different insect species, along with the 10 PGRP amino acid sequences from D. kikuchii. Phylogenetic analysis revealed that the DkikPGRP genes of D. kikuchii are distributed across distinct evolutionary branches and share high homology with PGRP genes from other insects, suggesting a close evolutionary relationship between the PGRP genes of D. kikuchii and those of other insect species. Transcriptome profiling revealed that DkikPGRP-S1, -S2, -S3, -S4, and -S5 were upregulated in the midgut, fat body, and hemolymph after Bt infection, showing tissue- and time-specific immune responses. Functional assays using siRNA knockdown demonstrated distinct roles of DkikPGRP-S4 and DkikPGRP-S5: DkikPGRP-S5 mainly promoted antimicrobial peptide (AMP) expression, including attacin, lebocin, lysozyme, and cecropin, whereas DkikPGRP-S4 showed a complex regulatory pattern, enhancing lebocin and lysozyme but suppressing attacin without affecting gloverin or cecropin. Silencing either gene significantly increased larval mortality upon Bt challenge. These results highlight the specialized immune regulatory functions of PGRPs in D. kikuchii, provide new insights into host–pathogen interactions, and suggest potential molecular targets for sustainable pest management strategies. Full article

Most respiratory diseases are driven by excessive airway inflammation and oxidative stress, yet current therapies often lack durable efficacy or are unsafe. Host-defense peptides, commonly enriched in animal venoms, offer diverse, target-selective scaffolds for new therapeutics. In this study, we aimed to discover a novel bioactive peptide with therapeutic potential on respiratory tract damage by utilizing Nephila clavata venom gland transcriptome. Using in silico analysis and machine learning-based functional prediction, we designed a peptide, NC-CV, expected to have dual anti-inflammatory and antioxidant activities with low cytotoxicity. In experimental validation, NC-CV improved human bronchial epithelial BEAS-2B cell viability under lipopolysaccharide (LPS) exposure while reducing LPS-induced pro-inflammatory cytokine expression and intracellular reactive oxygen species (ROS) generation. Mechanistic studies and molecular docking simulations indicated that NC-CV prevents toll-like receptor 4 signaling activation, suppressing nuclear factor κB and mitogen-activated protein kinase pathways. Moreover, the antioxidant activity of NC-CV was primarily based on direct intracellular ROS scavenging rather than the induction of endogenous antioxidant enzymes. Collectively, these findings demonstrated that the venom-derived peptide NC-CV disrupts the self-reinforcing cycle involving inflammatory signaling and oxidative stress in airway epithelium, highlighting its promise as a therapeutic candidate for respiratory disease. Full article

Thioester-containing proteins (TEPs), which are distinguished by the thioester motif (GCGEQ), are essential to arthropods’ defense against infections. Although TEPs have been extensively investigated in Anopheles, Aedes, and Drosophila, their functions in Culex mosquitoes remain inadequately explored. Interestingly, we discovered that Culex TEPs exhibit functional antagonism to their orthologs in other species, actively facilitating viral infection in this vector. In this study, we identified nine TEP genes in Culex quinquefasciatus, three of which were found to critically facilitate Japanese encephalitis virus (JEV) infection, with CqTEP27 exhibiting the most pronounced proviral effect. Mechanistically, CqTEP27 may have suppressed the production of several antimicrobial peptides (AMPs), which increased JEV replication. Our work also highlights the potential of targeting susceptibility factors such as CqTEP27 to block pathogen acquisition. Notably, the rate of mosquito infection was significantly decreased by membrane blood feeding antisera against CqTEP27. Therefore, vaccination against CqTEP27 offers a workable method of avoiding JEV infection. According to our research, CqTEP27 is a promising target for the development of vaccines that prevent JEV transmission. By preventing viral infection in mosquitoes that feed on immunized hosts, this approach can directly disrupt the natural transmission cycle, offering a novel strategy to reduce the disease burden. Full article

Fusarium verticillioides, a hemibiotrophic pathogen, infects a range of important crops and contaminates grains with fumonisin B1 (FB1) toxins, posing serious threats to yield, quality, and food safety. Secreted proteins containing Common Fungal Extracellular Membrane (CFEM) domains are known to contribute to the pathogenicity of several fungi, yet their functions in F. verticillioides remain poorly understood. In this study, we first identified the truncated protein FvCfem7^ΔSP without signal-peptide-triggered host immune responses in tobacco. The knockout mutant ΔFvcfem7 exhibited significantly enhanced virulence, while the constitutive overexpression of the FvCFEM7-OE strain showed reduced pathogenicity. Notably, foliar spraying of recombinant FvCfem^ΔSP protein suppressed fungal infection. FvCfem7 accumulated specifically in haustorium-like structures during early infection of maize leaves and onion. However, heterologous expression of FvCfem^ΔSP in Nicotiana benthamiana leaves and maize protoplasts can be localized in their cytoplasm and nucleus, although its potential transport mechanism remains to be elucidated. Further analysis revealed that FvCfem7 interacts with specific members of ZmPR5, as well as ZmPR1 and ZmPR4. The ΔFvcfem7 mutant suppressed ZmPR1 induction while enhancing ZmPR5 expression at 24 hpi, which suggests that FvCfem7 modulates the expression of PR proteins at the early invasion stage. In summary, FvCfem7 was identified as a CFEM effector that is recognized and hijacked by PR proteins, thereby triggering immune defenses, while its host-targeting function was also characterized. Full article

Background: Periodontitis is a multifactorial inflammatory disease influenced by immune and genetic factors. Certain genetic and immunological disorders, such as Down syndrome (DS), Leukocyte Adhesion Deficiency type I (LAD-I), and Papillon–Lefèvre syndrome (PLS), are associated with early-onset and severe periodontitis. Understanding their molecular and immunological mechanisms is crucial for advancing personalized therapeutic approaches. Methods: A systematic review was conducted following PRISMA 2020 guidelines to compare inflammatory gene expression profiles in patients with periodontitis associated with genetic or immune-mediated disorders and those without systemic conditions. Searches were performed in PubMed, Scopus, Web of Science, and Embase for studies published between 2010 and June 2025. Eligible studies reporting cytokine profiles or inflammatory gene expression were included and analyzed. Results: Six case–control studies met the inclusion criteria: three on DS, two on LAD-I, and one on PLS. DS patients showed increased serum levels of IL-1 beta, TNF-alpha, IL-4, IL-10, and IFN-gamma, with dysregulation of STAT1, STAT3, and SOCS3. LAD-I was characterized by overexpression of IL-17A, IL-6, IL-23, G-CSF, CXCL2, and CXCL5, indicating IL-17–driven inflammation and excessive neutrophil activation. In PLS, cathepsin C deficiency impaired activation of the antimicrobial peptide LL-37, leading to compromised host defense and accelerated tissue breakdown. Conclusions: Patients with periodontitis linked to genetic or immune-mediated disorders exhibit distinct inflammatory gene expression signatures that enhance disease susceptibility and progression. Identifying these immunoinflammatory pathways may guide precision periodontal therapies, although larger, standardized studies are required to validate these findings. Full article

Besnoitia besnoiti is an apicomplexan parasite responsible for bovine besnoitiosis, a debilitating disease in cattle resulting in local and systemic clinical signs with detrimental effects on reproductive performance and productivity in livestock. Fast-replicating tachyzoites and slowly proliferating bradyzoites elicit an excessive host innate immune response, mainly by activated polymorphonuclear neutrophils (PMN), which extrude neutrophil extracellular traps (NETs) as a defense mechanism. These PMN-derived structures, composed principally of DNA, histones, and peptides, play a crucial role not only in parasite entrapment but also in NET-associated endothelial damage, thereby most likely contributing to the pathogenesis of this neglected cattle parasitosis. Uncontrolled production of NETs or their inadequate removal may perpetuate an inflammatory environment in the vasculature and epidermis. Thus, novel alternative treatment of animals with chronic bovine besnoitiosis displaying severe clinical manifestations such as hyperkeratosis, vulvovaginitis and orchitis, could be considered for future study to either hampering NETs release or reducing NETs concentrations in affected tissues. Since effective treatments and control strategies for bovine besnoitiosis do not yet exist, this review serves as a guide for further research on the metabolic signature, signaling pathways, receptors, and pathogenesis of B. besnoiti-triggered NETs formation, providing insights into potential therapeutic approaches to avoid excessive NETs extrusion. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with immune dysregulation, skin barrier dysfunction, and microbial dysbiosis characterized by Staphylococcus aureus overcolonization and reduced bacterial diversity. Beyond its classical role in calcium homeostasis, Vitamin D (VD) influences skin immunity and microbial composition. This review summarizes current knowledge on VD metabolism, its immunological pathways in AD, and its interactions with the skin microbiome. Recent evidence positions the skin as an active immunological organ rather than a passive barrier. Commensal bacteria such as Staphylococcus epidermidis not only inhibit pathogens by producing bacteriocins and modulins but also generate ceramides and short-chain fatty acids (SCFAs) that stabilize the lipid barrier. Moreover, dermal fibroblasts and preadipocytes produce antimicrobial peptides, while resident γδ T cells release growth factors like fibroblast growth factor 7 (FGF7), linking host defense with tissue regeneration. VD modulates AD by suppressing T helper 2 cells/T helper 17 cell responses, enhancing regulatory T cell development, inducing antimicrobial peptides, and strengthening skin and gut barrier integrity. Its interaction with the microbiome and pathways such as SCFA and aryl hydrocarbon receptor (AhR) signaling supports its potential as an adjunctive therapy in AD management. Evidence from mechanistic studies and animal models suggests that VD supplementation may modulate inflammation and microbial diversity. Clinical implications, therapeutic perspectives, and future research directions highlight the potential of VD as a therapeutic adjunct in AD management. Full article

The domesticated silkworm, Bombyx mori, is a highly valued biodiversity and economic asset, acclaimed for its silk production, besides making important contributions to various scientific disciplines. However, the sericulture industry faces ongoing threats from bacterial and viral infections, which severely impact silkworm health and silk yield. This review provides a comprehensive overview of the innate immune response of B. mori against bacterial and viral pathogens, emphasizing the fundamental molecular and cellular defense mechanisms. We explore the humoral and cellular immune response using antimicrobial peptides (AMPs), pattern recognition receptors (PRRs) like peptidoglycan recognition protein (PGRP), and glucan recognition protein (GRP), which activate canonical signaling pathways. The review further highlights the molecular mechanisms underlying the silkworm’s defense against viruses, incorporating RNA interference (RNAi), apoptosis, and distinct signaling pathways such as Toll and Imd, JAK/STAT, and STING. We also discussed the viral suppression strategies and modulation of host metabolism during infection. Furthermore, the review explores the recent use of CRISPR-Cas gene editing to enhance disease resistance, presenting a promising avenue for mitigating pathogen-induced losses in sericulture. By elucidating these mechanisms, the work provides a synthesis that is critical in terms of developing particular interventions and developing more resistant silkworm strains to ensure that the industry of sericulture becomes viable and productive. Full article

This study investigated the protective effect of fermented milk by Lacticaseibacillus rhamnosus D1 in a murine model of Typhoid fever, focusing on cytokines, antimicrobial peptides and microbiota modulation. BALB/c mice were pre-treated with milk fermented by L. rhamnosus D1 prior to Salmonella Typhimurium challenge. Outcomes assessed included survival, weight change, bacterial translocation, mRNA expression of cytokines and antimicrobial peptides, in addition to gut microbiota modulation. Mice receiving fermented milk exhibited higher survival rates, reduced bacterial translocation and attenuated weight loss compared to controls. mRNA expression analyses revealed that L. rhamnosus D1 pre-treatment suppressed the expression of pro-inflammatory cytokines (IFN-γ, IL-6 and IL-12) and upregulated anti-inflammatory cytokines (IL-5, IL-10 and TGF-β), as well as antimicrobial peptides (Reg3β, Reg3γ and Lcn2). Furthermore, we observed that the consumption of fermented milk changed the gut microbiota of infected mice, not only by modulating the existing taxa, but also by facilitating the emergence of unique, potentially beneficial microbial lineages, such as Muribaculum, Roseburia, Intestinimonas, Bdellovibrio and Facklamia. These findings indicate that L. rhamnosus D1 protected mice against S. Typhimurium infection through immunomodulatory and microbiota-mediated mechanisms, changing mucosal immunity and strengthening the intestinal barrier by modulating gut microbiota and immune responses, in addition to promoting host antimicrobial defenses. Full article

Defensins are a class of small cysteine-rich cationic antimicrobial peptides (AMPs) that play vital roles in immune-regulating insect–microbe interaction, offering great potential for developing pest control approaches using RNA interference (RNAi) and insect pathogens. However, the biocontrol potential of defensins from the destructive rice pest Nilaparvata lugens (brown planthopper, BPH) remains largely unexplored. Here, we identified and functionally characterized a defensin-encoding gene NldefB in BPH. The open reading frame (ORF) of NldefB is 315 bp in length, encoding 104 amino acids with a conserved Knot1 domain. The qRT-PCR results showed that the transcription level of NldefB went upward with the increasing developmental stages, with the highest expressions in the female adults and their fat body. The expression of NldefB was continuously induced by bacterial pathogens but exhibited a pattern of initial increase followed by a decrease when challenged by a fungal pathogen Metarhizium anisopliae. RNAi-mediated silencing of NldefB significantly decreased the host survival rate, egg production and hatchability, as well as the capability to resist fungal infection. Additionally, NldefB suppression resulted in a significant increase in microbial loads. Our findings underscored that NldefB plays essential roles in regulating host development, pathogen defense, and microbial maintenance, providing a potential target for RNAi- and microbe-mediated BPH biocontrol. Full article

Antimicrobial peptides (AMPs), also referred to as host defense peptides, are promising molecules in the development of the next generation of antibiotics against drug-resistant bacterial pathogens. Thanatin comprises a family of naturally occurring cationic AMPs derived from several species of insects. The first thanatin, 21 residues long, was identified from the spined soldier bug, and more thanatin peptides have been discovered in recent studies. The 16-residue thanatin from Anasa tristis, or Ana-thanatin, represents the shortest sequence in the family. However, the antimicrobial activity and mechanistic process underpinning bacterial cell killing have yet to be reported for Ana-thanatin peptide. In this work, we examined the antibacterial activity, structures, and target interactions of Ana-thanatin. Our results demonstrated that Ana-thanatin exerts potent antibiotic activity against strains of Gram-negative and Gram-positive bacteria. Biophysical studies demonstrated that Ana-thanatin interacts with LPS outer membrane and can permeabilize the OM barrier in the process. Atomic-resolution structures of the peptide in free solution and in complex with lipopolysaccharide (LPS) micelle were solved by NMR, determining canonical β-sheet structures. Notably, in complex with LPS, the β-sheet structure of the peptide was better defined in terms of the packing of amino acid residues. Further, MD simulations demonstrated rapid binding of the Ana-thanatin peptide with the LPS molecules within the lipid bilayers. These studies have revealed structural features which could be responsible for LPS-OM disruption of the Gram-negative bacteria. In addition, NMR heteronuclear single quantum coherence (HSQC) studies have demonstrated that Ana-thanatin can strongly interact with the LPS transport periplasmic protein LptA_m, potentially inhibiting OM biogenesis. Taken together, we surmise that the Ana-thanatin peptide could serve as a template for the further development of novel antibiotics. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most devastating infectious diseases worldwide, with rising multidrug resistance limiting the effectiveness of conventional treatments. Novel therapeutic approaches are urgently needed to complement or replace existing regimens. Among emerging candidates, antimicrobial peptides (AMPs) stand out as versatile molecules capable of exerting direct antimycobacterial effects while also modulating the host immune response. This review explores peptide-based strategies against TB, with a focus on four major axes of innovation. First, we examine host-directed pathways, including the vitamin D–cathelicidin axis and other immunomodulatory mechanisms and their regulatory role in the induction of endogenous AMPs such as cathelicidin LL-37, which contributes to host-directed defense. Second, we discuss peptide-based vaccines designed to elicit robust and durable protective immunity, representing a complementary alternative to classical vaccine approaches. Third, we highlight the synergistic potential of AMPs in combination with first-line and second-line anti-TB drugs, aiming to restore or enhance bactericidal activity against resistant strains. Finally, we analyze technological platforms, including nanocarriers and inhalable formulations, that enable targeted pulmonary delivery, improve peptide stability, and enhance bioavailability. By integrating molecular design, immune modulation, and advanced delivery systems, peptide-based strategies provide a multifaceted approach to overcoming the limitations of current TB therapy. Collectively, these advances position AMPs not only as promising standalone agents but also as key components in combination and host-directed therapies, with strong potential to reshape the future clinical management of tuberculosis. Full article