Search Results (192)

Defensins, one of the members of the antimicrobial peptide family, play a vital role in resisting microbial invasion and immune regulation. Porcine β-defensin 2 possesses excellent stability, making it an ideal antibiotic alternative for feed additives. In this study, a total of 15 piglets were used to investigate the effects of supplementing diets with 2.5 mg/kg (LP group) and 5 mg/kg (HP group) of pBD2 to weaned piglets. The results revealed that pBD2 significantly increased the total weight gain and average daily weight gain (p < 0.05), the contents of T-AOC, SOD, IgM, and IL-10 in serum (p < 0.05), the villus-to-crypt ratios, and the expression of tight-junction proteins ZO-1 and claudin-1 (p < 0.05) in the small intestine. Furthermore, pBD2 increased the abundance of beneficial bacteria related to nutrient and energy metabolism while decreasing the abundance of harmful bacteria associated with intestinal inflammation and diarrhea. Alterations in the gut microbiota were closely associated with the levels of T-AOC, SOD, IgM, and IL-10 in serum. pBD2 primarily enhanced the health of weaned piglets by influencing antioxidant capacity, intestinal barrier function, and the intestinal microbiota. Our research provides a novel perspective for addressing the issue of antibiotic residues in feed. Full article

Objectives: The oral cavity hosts one of the most complex microbial communities in the body. A disruption of the balance favors the growth of pathogenic species, contributing to oral diseases. The rise in microbial resistance has limited the effectiveness of conventional treatments, shifting the interest to natural product-based alternatives. Given its superior bioavailability and bioactivity in other models, this study investigates the antifungal potential of a novel curcumin derivative, PAC (3,5-bis(4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone), and studies its impact on host–pathogen dynamics and host defense mechanisms. Methods: Candida albicans was used as the model organism. Viability, growth kinetics, and colony formation were evaluated using optical density, agar culture, and MTT assay. Biofilm formation was assessed through electron microscopy and total sugar quantification. The morphological transition from hyphae to the less virulent blastospore was monitored using an optical microscope. The gene expression of adhesion factors and host defense markers was analyzed using RT-PCR. Results: PAC impairs C. albicans viability and reduces virulence by compromising biofilm formation and ensuring phenotypic transition to a blastospore form. Also, PAC controls C. albicans growth via necrosis/ROS pathways. As a result, PAC appears to repress host–pathogen interaction by downregulating SAPs, EAP1, and HWP1 adhesion genes, thus relieving the need to activate gingival epithelial cell defense mechanisms. This is highlighted by recording baseline levels of IL-6, IL-8, and IL-1β cytokines and antimicrobial β-defensin peptides in the presence of less virulent candida forms. Conclusions: PAC effectively reduces C. albicans virulence by limiting biofilm formation and adhesion while minimizing inflammatory responses. These findings support its potential as a promising therapeutic agent for infectious disease control. Full article

Enterotoxigenic Escherichia coli (ETEC), a common intestinal pathogen, can colonize the intestines and induce diarrhea in piglets, which brings great economic losses to the swine industry. Antibiotics are recommended to the treatment for diarrhea caused by ETEC in weaned piglets. However, with the emergence and spread of multidrug-resistant ETEC, there is an urgent need to develop alternatives to antibiotics. Due to the unique antibacterial mechanism of targeting bacterial membranes, antimicrobial peptides (AMPs) are promising candidates. In this study, the activity of crude recombinant porcine β-defensin 2 (rPBD2) expressed in Pichia pastoris (P. pastoris) was measured in vitro. Mice infected with ETEC were orally administered 16, 8, and 4 AU crude rPBD2 for 7 consecutive days to evaluate its anti-infective activity in vivo. The results showed that in addition to broad antibacterial activity against Gram-positive and -negative bacteria, crude rPBD2 displayed high tolerance to temperatures ranging from 20 to 60 °C, a broad range of pH, trypsin, pepsin, and physiological concentrations of salts. In an ETEC-induced mouse model, the oral administration of crude rPBD2 decreased diarrhea scores and the intestinal/carcass ratio and alleviated body weight loss. Additionally, crude rPBD2 decreased bacterial loads in stools and the colon (HP group), and the levels of serum pro-inflammatory cytokines IL-6 (HP group) and TNF-α (HP and MP groups), and increased the villus height and the ratio of villus height to crypt depth (VH/CD) in the ileum (HP and MP groups). Our study provides a cost-effective way for PBD2 production and identifies it as a promising candidate to combat ETEC-induced infection. Full article

Background/Objectives: β-defensins are a family of classical endogenous antimicrobial peptides involved in innate immune response. β-defensins are encoded by a large number of loci and known to show extensive copy number variations (CNVs) that may be useful as DNA markers for host resilience against pathogenic infections. Methods: We developed a quantitative PCR-based method to estimate the genomic copy numbers of 13 pig β-defensin (pBD) genes and analyzed the range and extent of CNVs across several commercial pig breeds. Results: We assessed 38 animals from four pure breeds and a crossbreed and observed CNVs ranging from two to five genomic copies from pBD114, pBD115, pBD119, pBD124, pBD128, and pBD129, indicating extensive individual variations of gene copy numbers of these genes within each breed. The mean copy numbers of these pBDs were lower in Landrace and higher in Berkshire than in other breeds. We also observed a strong correlation between the genomic copy number and their expression levels with the correlation coefficient (r) > 0.9 for pBD114, pBD119, and pBD129 in the kidney, with these genes being highly expressed. Conclusions: Although we only analyzed 13 pBDs among 29 reported genes, our results showed the presence of extensive CNVs in β-defensins from pigs. The genomic copy number of β-defensins may contribute to improving animal resilience against pathogenic infections and other associated phenotypes. Full article

(1) The aim of this study was to elucidate the role of the Gallus gallus avian β-defensin 11 (AvBD11) in the immune response induced by the avian influenza virus H9N2. (2) AvBD11 was expressed using E. coli, and the effects of different concentrations of AvBD11 on cytokine expression in the ex vivo and in vivo erythrocytes of chickens infected with the avian influenza subtype H9N2 were detected by using fluorescence quantification. (3) The results showed that cytokine expression varied among the test groups compared to the control group in the in vitro assay at 2, 6, and 10 h. Lipopolysaccharide induced TNF factor (LITAF) and Interferon-γ (IFN-γ) were significantly increased in the AvBD11 group with the addition of the final concentration of 15 μg/mL at 6 h. At 10 h, Interleukin-1β (IL-1β) and IFN-γ were both more significantly increased in the 15 and 10 μg/mL groups than in the H9N2 group alone. In the in vivo test, IFN-γ and Interleukin-10 (IL-10) were significantly increased in the high-dose group than in the H9N2 group at 3 d and 7 d. (4) In conclusion, the ability of AvBD11 to induce the expression of more cytokines by chicken erythrocytes in a short period of time suggests that it is not only an antimicrobial peptide but also a possible immunomodulator. Full article

The physiological functions of newborn calves are undeveloped, especially the immune system, making them susceptible to infections. In recent years, the theory of trained immunity has attracted attention and provided new strategies to prevent unknown infections in animals. This study investigated the effects of feeding yeast β-glucan on the intestinal and respiratory health of calves during the suckling period. Newborn Holstein calves (average birth weight: 36.18 ± 0.61 kg, mean ± SE) were randomly assigned to two groups: the PO (Per Os) group (n = 22) and the CON (Control) group (n = 22). Calves in the PO group were fed a yeast β-glucan solution (0.1 g/mL, 65 mg/kg body weight) at 3 and 6 days of age, respectively, while calves in the CON group received equal volumes of sterile saline orally at the same time. Blood and fecal samples were collected at 7 and 30 days of age, respectively. The results showed that (1) Compared to the CON group, being fed yeast β-glucan resulted in an inflammatory response after 24 h of the second administration, including increased gene expression of interleukin-6 (IL-6, p < 0.01), interleukin-1 beta (IL-1β, p < 0.01), and malonaldehyde (MDA, p < 0.001) content. Also, stimulation with β-glucan increased the concentrations of secreted immunoglobulin A (sIgA, p < 0.01) and defensins (p < 0.05) in the rectal feces. (2) Pre-stimulation with yeast β-glucan effectively reduced the incidence of diarrhea (p < 0.05) and bovine respiratory disease (BRD, p < 0.05) from day 31 to day 60. (3) At 30 days of age, the pre-stimulated calves had significantly lower serum DAO (p < 0.001) and MDA levels (p < 0.05), while they had higher levels of serum IL-6 (p < 0.01) and fecal slgA (p < 0.05) than calves in the CON group. (4) Pre-stimulation with yeast β-glucan altered the intestinal bacterial community; the Beta diversity results showed that the CON group and the PO group were clustered separately in the principal coordinate analysis (PCoA) graph. Obviously, the PO group sample points were more clustered. In conclusion, this study highlights the potential of yeast β-glucan-induced trained immunity to improve calf health during the suckling period. The findings offer new insights into the prevention of intestinal and respiratory infections in calves. Full article

This study aimed to evaluate the intrinsic in vitro performance of naïve porcine prepubertal Sertoli cells (SCs) and SCs loaded with blank poly(lactic acid) microparticles (MP) or amphotericin B poly(lactic acid) microparticles (AmB-MP) against Candida tropicalis, a prevalent pathogenic non-albicans species. The objective was to assess their impact on biofilm formation and the cellular response mechanisms involved, building on previous findings that highlight SCs’ potential as anti-infective agents and drug carriers. Our results demonstrated that SCs successfully internalized Candida tropicalis while maintaining viability and exhibited a strong anti-infective effect, inhibiting biofilm formation by 70%. This inhibition increased to 80–90% when SCs were combined with AmB-MP. The interaction between SCs (both naïve and MP-loaded) and Candida tropicalis triggered the activation of MAPK, AKT, and NF-kB signaling pathways, leading to the upregulated expression of innate immune factors such as MHC-II, TLR-4, TGF-β, IDO, and β-defensin 123. These findings reinforce the role of SCs in infection control and drug delivery. Furthermore, their anti-infective and scavenging activity is linked to a tolerogenic phenotype, suggesting a potential dual therapeutic role at the host–pathogen interface. Full article

Candida species, particularly Candida albicans, are causative agents of oral infections to which immunocompromised patients are especially susceptible. Reduced saliva flow (xerostomia) can lead to Candida overgrowth, as saliva contains antibacterial components such as histatins and β-defensins that inhibit fungal growth and adhesion to the oral mucosa. Candida adheres to host tissues, forms biofilms, and secretes enzymes required for tissue invasion and immune evasion. Secretory asparaginyl proteinases (Saps) and candidalysin, a cytolytic peptide toxin, are vital to Candida virulence, and agglutinin-like sequence (Als) proteins are crucial for adhesion, invasion, and biofilm formation. C. albicans is a risk factor for dental caries and may increase periodontal disease virulence when it coexists with Porphyromonas gingivalis. Candida infections have been suggested to heighten the risk of oral cancer based on a relationship between Candida species and oral squamous cell carcinoma (OSCC) or oral potentially malignant disorder (OPMD). Meanwhile, β-glucan in the Candida cell wall has antitumor effects. In addition, Candida biofilms protect viruses such as herpesviruses and coxsackieviruses. Understanding the intricate interactions between Candida species, host immune responses, and coexisting microbial communities is essential for developing preventive and therapeutic strategies against oral Candida infections, particularly in immunocompromised individuals. Full article

Osteomyelitis, a severe bone infection, poses a significant therapeutic challenge in both human and veterinary medicine, especially due to the increasing prevalence of antibiotic-resistant pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Conventional treatments, including surgical debridement and systemic antibiotics, often prove inadequate due to the ability of bacteria to form biofilms and evade host immune responses. Antimicrobial peptides (AMPs), such as LL-37 and β-defensins, have emerged as a promising alternative therapeutic strategy. AMPs exhibit broad-spectrum antimicrobial activity, including efficacy against resistant strains, and possess immunomodulatory properties that can promote bone regeneration. This article comprehensively reviews AMP applications in treating osteomyelitis across both human and veterinary medicine. We discuss diverse therapeutic approaches, including free AMPs, their conjugation with biomaterials such as collagen and chitosan to enhance delivery and stability, and the development of AMP-based nanoparticles. Furthermore, we analyze preclinical and clinical findings, highlighting the efficacy and safety of AMPs in combating osteomyelitis in both human and animal patients. Finally, we explore future perspectives and challenges, such as optimizing delivery, stability, and efficacy, while minimizing cytotoxicity, and in translating AMP-based therapies into clinical practice to effectively manage this debilitating disease. Full article

Antimicrobial peptides, such as beta-defensin 2 (BD2), are vital in controlling infections and immune responses. In this study, we investigated the expression and role of BD2 in the amniotic membrane and human amniotic epithelial cells (hAECs) from patients with preterm birth and chorioamnionitis, focusing on its regulation of inflammatory cytokines and its protective effect on the epithelial barrier. Our results show increased BD2 expression in chorioamnionitis, and Lipopolysaccharide (LPS)-induced inflammation increased BD2 release from hAECs in a dose- and time-dependent manner. BD2 treatment effectively modulated the inflammatory response by reducing pro-inflammatory cytokines (IL-6, IL-1β) and enhancing the release of the anti-inflammatory cytokine IL-10. Additionally, BD2 helps preserve epithelial barrier integrity by restoring E-cadherin expression and reducing Snail expression in inflamed hAECs. In an LPS-induced preterm birth mouse model, BD2 treatment delayed preterm delivery and reduced inflammatory cytokine levels. These results suggest that BD2 plays a protective role in preventing preterm birth by regulating inflammation and maintaining epithelial barrier function, highlighting its therapeutic potential for inflammation-related preterm birth. Full article

In addition to its classical role in calcium and phosphate metabolism regulation, vitamin D also has an important impact on immunity modulation. Vitamin D regulates the immune response, shifting from a proinflammatory state to a more tolerogenic one by increasing the release of anti-inflammatory cytokines while downregulating proinflammatory cytokines. Thus, low levels of vitamin D have been associated with an increased risk of developing autoimmune diseases like multiple sclerosis and type 1 diabetes. Furthermore, this prohormone also enhances the release of well-known antimicrobial peptides, like cathelicidin LL-37 and β-defensins; therefore, it has been proposed that vitamin D serum levels might be related to the risk of well-known pathogen infections, including herpesviruses. These are a group of widely spread viral pathogens that can cause severe encephalitis or tumors like Kaposi’s sarcoma and Burkitt lymphoma. However, there is no consensus on the minimum levels of vitamin D or the recommended daily dose, making it difficult to establish a possible association between these two factors. This narrative non-systematic review will analyze the mechanisms by which vitamin D regulates the immune system and recent studies about whether there is an association between vitamin D serum levels and herpesvirus infections. Full article

Research on the immunological development of lymphoid organs in chicks has been extensive, yet a significant gap exists in our understanding of innate immunity during embryonic life within the intestinal tract. This study investigated the developmental trajectory of intestinal immunity in chick embryos by evaluating basal gene expression levels of key immune markers at embryonic days (ED) 14, 17, and 20. The results indicated variable expression levels of cytokines, antimicrobial peptides (AMPs), and Toll-like receptor (TLRs) genes throughout the intestinal tract. Most cytokines and chemokines exhibited elevated expression in the cecum, while AMPs, including avian-β-defensins (AvBDs) and cathelicidins (CATHs) genes, showed increased levels in the jejunum at ED20. The findings from the developmental trajectory analysis of these genes revealed elevated expression levels of cytokines, including interferon (IFN)-γ, interleukin (IL)-6, IL-13, and transforming-growth factor (TGF)-β in the cecum at ED20. However, no consistent patterns were observed for AvBDs, CATHs, and TLRs, as their expression varied across different developmental stages of the chick embryo. These findings significantly contribute to our understanding of intestinal immune system development in chick embryos and provide a foundation for further research aimed at enhancing immune capabilities, especially in segments with lower expression levels of immunomodulatory genes. Full article

Inappropriate and excessive use of antibiotics is responsible for the rapid development of antimicrobial resistance, which is associated with increased patient morbidity and mortality. There is an urgent need to explore new antibiotics or alternative antimicrobial agents. S. aureus a commensal microorganism but is also responsible for numerous infections. In addition to innate resistance to β-lactam antibiotics, S. aureus strains resistant to methicillin (MRSA) often show resistance to other classes of antibiotics (multidrug resistance). The advancement of phage therapy against MRSA infections offers a promising alternative in the context of increasing antibiotic resistance. Therapeutic phages are easier to obtain and cheaper to produce than antibiotics. However, there is still a lack of standards to ensure the safe use of phages, including purification, dosage, means of administration, and the quantity of phages used. Some bacteria have developed defense mechanisms against phages. The use of phage cocktails or the combination of antibiotics and phages is preferred. For personalized therapy, it is essential to set up large collections to enable phage selection. In the future, the fight against MRSA strains using phages should be based on a multidisciplinary approach, including molecular biology and medicine. Other therapies in the fight against MRSA strains include the use of endolysin antimicrobial peptides (including defensins and cathelicidins). Researchers’ activities also focus on the potential use of plant extracts, honey, propolis, alkaloids, and essential oils. To date, no vaccine has been approved against S. aureus strains. Full article

Background/Objectives: Human β-defensin 2 (HBD2) is a protein that plays an important role in activating the immune system by modulating spinal pathways and the inflammatory response. According to previous research, HBD2 was proven to be important in chronic spontaneous urticaria (CSU) (their values were significantly elevated in CSU patients, with a significant correlation between HBD2 levels and the percentage of peripheral basophils, suggesting that elevated HBD2 levels may be a potential marker of basophil and mast cell activation), which led us to additional research on the HBD2 molecule in isolated chronic angioedema. The aim of this research is to examine HBD2 values in the saliva and serum of patients with isolated angioedema, as a potential biomarker of the disease. Methods: This cross-sectional study involved a total of 102 participants, involving three groups: 33 patients with isolated chronic non-hereditary angioedema (AE) (defined as sudden onset of localized edema without chronic urticaria), 33 patients with angioedema associated with chronic urticaria (CU+AE), and 35 healthy participants (controls, CTRL). They provided a saliva sample to determine HBD2 levels using an ELISA (Enzyme-Linked Immunosorbent Assay). Subsequently, a peripheral blood sample (serum) was taken from the participants to determine HBD2 levels using the same ELISA. Results: Salivary HBD2 levels were significantly higher in those with CU+AE than in the CTRL (p = 0.019). While salivary HBD2 values differed between those with angioedema and CTRL, the serum HBD2 values did not. Also, no correlation between the levels of HBD2 in saliva and serum was found. Conclusions: Since we found that salivary HBD2 values were significantly higher in those with CU+AE than in CTRL, this points to a possible role of the HBD2 molecule in pathogenesis of AE (namely, that it induces degranulation in mast cells and vascular permeability, and has antimicrobial properties) Therefore, more research is needed to determine how reliable salivary HBD2 measurement is, as well as its significance. Full article

Today, Candida albicans is still the most common cause of both local and life-threatening systemic candidiasis. The spread of resistant fungal strains has resulted in an urgent need to search for new promising antimycotics. Here, we investigated the antifungal action of the tobacco defensin NaD1 against susceptible and resistant to azoles and echinocandins strains of C. albicans. We demonstrated that NaD1 was equally effective and fungicidal against all tested strains. The MIC and MFC values were 6.25 and 12.5 µM, respectively. We showed for the first time that NaD1 could act synergistically not only with caspofungin but also with human host defense antimicrobial peptides cathelicidin LL-37 and β-defensin-2 (HBD2) against susceptible and resistant fungal strains. Using flow cytometry, we demonstrated that NaD1 in combinations with LL-37 or HBD2 can reinforce each other by enhancing membrane disruption. Using the Caco-2 cell monolayer model, we demonstrated that NaD1 impaired the adhesion of C. albicans cells to the human epithelium. Moreover, NaD1 inhibited the formation of fungal biofilms in Sabouraud broth and less markedly in nutrient-rich RPMI-1640 medium, and enhanced the antibiofilm activity of caspofungin. Thus, we hypothesized that NaD1 might affect the development of candidiasis in vivo, including that caused by resistant fungal strains. Full article