Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Commentary: One mechanism of Sishen Pill on diarrhea with kidney Yang deficiency syndrome: influencing metabolic function by intestinal microorganisms and enzyme activity mediates the gut-kidney axis.","authors":"Junren Yao, Jiang Lin, Yichuan Xv","doi":"10.3389/fcimb.2025.1690941","DOIUrl":"10.3389/fcimb.2025.1690941","url":null,"abstract":"","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1690941"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology and antimicrobial resistance of pathogens in pediatric sinus infections: a retrospective study at a Japanese otolaryngology clinic (2023-2025).","authors":"Shiori Kitaya, Toshiaki Kikuchi, Kazuhiro Nomura, Yuri Nomura, Ryoukichi Ikeda, Hajime Kanamori, Yukio Katori","doi":"10.3389/fcimb.2025.1662544","DOIUrl":"10.3389/fcimb.2025.1662544","url":null,"abstract":"<p><strong>Introduction: </strong><i>Haemophilus influenzae</i> and <i>Streptococcus pneumoniae</i> are two of the major pathogens responsible for pediatric rhinosinusitis. Rising antimicrobial resistance (AMR) and pneumococcal serotype replacement have complicated treatment decisions. This study aimed to investigate bacterial distribution and AMR patterns in nasal discharge samples from children at a Japanese otolaryngology clinic.</p><p><strong>Methods: </strong>We conducted a retrospective study at an otolaryngology clinic in Sendai, Japan, from February 2023 to March 2025. A total of 2009 nasal discharge specimens were analyzed. Bacterial identification and antimicrobial susceptibility testing were performed according to Clinical and Laboratory Standards Institute guidelines. <i>H. influenzae</i> and <i>S. pneumoniae</i> were phenotypically classified and stratified by age (0-2, 3-5, and 6-13 years). Age-group comparisons were performed using Fisher's exact test with Holm correction.</p><p><strong>Results: </strong>Pathogens were detected in 1862 samples (92.7%). The most frequently isolated organisms were <i>Moraxella catarrhalis</i> (30.9%), <i>H. influenzae</i> (23.0%), and <i>S. pneumoniae</i> (20.6%). Among the 697 <i>H. influenzae</i> isolates, 44.8% were ampicillin-resistant, and 31.3% of all isolates were β-lactamase-negative ampicillin-resistant (BLNAR) strains. Some BLNAR strains exhibited reduced susceptibility to amoxicillin-clavulanic acid (MIC₉₀ = 8 μg/mL). Cefotaxime, cefditoren, and levofloxacin remained highly active. Among the 625 <i>S. pneumoniae</i> isolates, 66.6% were penicillin-susceptible, 31.0% were intermediate, and 2.4% were resistant; resistance to clarithromycin was observed in 84.3% of isolates. The prevalence of <i>Staphylococcus aureus</i> increased with age, with 25% of isolates in the 6-13-year group identified as methicillin-resistant.</p><p><strong>Conclusion: </strong><i>H. influenzae</i> and <i>S. pneumoniae</i> remain key pathogens in pediatric rhinosinusitis and exhibit high AMR rates. Age-specific trends, including increased methicillin-resistant <i>S. aureus</i> in older children, should guide empiric therapy. Ongoing AMR surveillance and culture-based management are essential.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1662544"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and performance evaluation of a clinical metagenomics approach for identifying pathogens in the whole blood from patients with undifferentiated fever.","authors":"Jan Slunečko, Rok Kogoj, Samo Zakotnik, Alen Suljič, Nataša Knap, Martin Bosilj, Franc Strle, Tatjana Avšič-Županc, Petra Bogovič, Miša Korva","doi":"10.3389/fcimb.2025.1667422","DOIUrl":"10.3389/fcimb.2025.1667422","url":null,"abstract":"<p><strong>Introduction: </strong>Blood culture is the cornerstone of microbiological diagnostics for patients with acute undifferentiated fever and no obvious localization of infection; however, up to 50% of cases remain undiagnosed. Infections caused by arboviruses, fastidious or even uncultivable bacteria, or parasites often go undiagnosed without the use of target-specific molecular methods. These are typically performed in a stepwise manner, increasing cost and delaying results. Metagenomic next-generation sequencing (mNGS) has recently gained recognition as a potential universal pathogen detection tool for such cases. Our study aimed to develop a streamlined mNGS workflow for simultaneous detection of intracellular and cell-free pathogens within a single sequencing library.</p><p><strong>Methods: </strong>Total nucleic acid was isolated separately from 200 EDTA blood samples. The plasma isolate was processed with DNase, followed by the depletion of host ribosomal and messenger RNA, reverse transcription, and sequence-independent single primer amplification (SISPA). The whole blood isolate was only reverse transcribed, with no other pre-processing manipulation. Finally, the two fractions were combined prior to library preparation and sequencing using either Oxford Nanopore Technologies or Illumina. Following established bioinformatics analysis, we developed a mathematical ranking approach (ClinSeq score) that enabled quick identification of relevant pathogens in approximately one hour.</p><p><strong>Results: </strong>The mNGS workflow reached 79.5% (159/200) overall sensitivity. For bacteria the sensitivity was 88.6% (70/79), DNA viruses, 66.7% (10/15) and for RNA viruses 73.8% (76/103). Pathogen detections by individual sequencing methods showed overall sensitivity of Illumina and ONT to be 80.0% (76/95) and 79.1% (83/105) respectively. The ClinSeq score correctly highlighted the pathogen in 126/200 (63.0%) samples effectively with a Cohen's kappa (<i>κ</i>) agreement of 0.61 with manual analysis.</p><p><strong>Conclusion: </strong>Developed comprehensive mNGS workflow detects a wide range of pathogens in patients with acute undifferentiated fever. The unified workflow improves sensitivity for intracellular bacteria and RNA viruses, reduces time, cost and complexity by eliminating the need for separate library preparations, enabling faster turnaround suitable for clinical settings. The ClinSeq score effectively differentiates true pathogen signals from background noise, reducing false positives and manual interpretation time. Overall, the workflow demonstrates flexible, and efficient pathogen detection, supporting its potential for clinical diagnostics and improved patient management.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1667422"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinnamaldehyde triggers cell wall remodeling and enhances macrophage-mediated phagocytic clearance of <i>Candida albicans</i>.","authors":"Zhaoling Shi, Jiajia Lin, Wenqian Li, Feng Chen, Wenna Zhang, Yue Yang, Kelong Ma","doi":"10.3389/fcimb.2025.1647320","DOIUrl":"10.3389/fcimb.2025.1647320","url":null,"abstract":"<p><strong>Introduction: </strong><i>Cinnamomum cassia</i>, a traditional Chinese medicinal herb, possesses cinnamaldehyde (CIN) with well-documented antifungal and immunomodulatory properties. Although CIN inhibits <i>Candida albicans</i> (<i>C. albicans</i>) growth, its role in macrophage-mediated clearance remains poorly understood.</p><p><strong>Methods: </strong>Here, we evaluated CIN's antifungal activity using MIC determination, spot assays, and time-growth curves. Cell wall disruption (β-glucan and chitin exposure) was assessed by transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), and flow cytometry.</p><p><strong>Results: </strong>Transcriptomic and functional enrichment analyses revealed that CIN compromises cell wall integrity by altering 123 differentially expressed genes (DEGs), particularly those governing hyphal development, cell wall biosynthesis, and biofilm formation. Specifically, CIN downregulated genes associated with β-glucan exposure, mannosylation, and chitin synthesis, and upregulated components of the Cek1/MAPK pathway. CIN-enhanced macrophage phagocytosis significantly increased fungal clearance and reduced fungal escape, as shown by flow cytometry, propidium iodide staining, and lactate dehydrogenase release assays. CIN-pretreated fungi activated the Dectin-1/Syk/CARD9/NF-κB cascade, leading to elevated pro-inflammatory cytokine secretion.</p><p><strong>Discussion: </strong>Mechanistically, CIN induces β-1,3-glucan exposure on <i>C. albicans</i>, thereby promoting Dectin-1-mediated phagocytosis and clearance. These findings provide an experimental basis for developing CIN as a novel antifungal therapeutic.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1647320"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of probiotic therapy in nonalcoholic fatty liver disease: mediating mechanism and future perspective.","authors":"Xing-Yu Luo, Wei-Bin Huang, Chuang-Hui Lu, Wu Gu, Zi-Xuan Feng, Sui Shen, Ming-Zheng Chen, Shu-Sen Zheng, Zhe Yang","doi":"10.3389/fcimb.2025.1638372","DOIUrl":"10.3389/fcimb.2025.1638372","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) has a global prevalence of 20%-33%, and has become the main cause of chronic liver disease. Apart from lifestyle modification therapy, there is currently no definitive pharmacological treatment, thus there is an urgent need to find effective intervention strategies to treat NAFLD. With the discovery of the important role of gut microbes in the pathogenesis of NAFLD, research on the prevention and treatment of non-alcoholic fatty liver disease by probiotics is increasing. At present, many studies have confirmed the role of probiotic regulation in the treatment of NAFLD, which can reduce the level of transaminase and liver fibrosis in patients and protect the liver. The clinical application of probiotics includes single species such as <i>Lactobacillus</i> and <i>Bifidobacteria</i>, as well as synbiotics with different compositions. This article reviews the therapeutic effects of probiotics on NAFLD and the mechanisms by which probiotics directly or indirectly affect the disease. Further research is needed to fully understand the specific underlying mechanisms between probiotics, gut microbes, and NAFLD, and more large-scale clinical trials are needed to evaluate probiotics for the treatment of NAFLD.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1638372"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic diversity and antibiotic resistance of <i>Mycobacterium bovis</i> in bovines in the Delta area of Egypt.","authors":"Mohamed Sabry A Elsayed, Zahraa H Alqaim, Aysam M Fayed, Samah Mahmoud Eldsouky, Mohamed Salah Basiouny, Azza M Metwally, Ahmed Abdelbadee, Al Shaimaa Hasan, Amira Kamal ElDin Mohammed ElAlfy, Mai Afifi Nasr, Shimaa Mostafa Elnahas Wahdan, Rasha Abdelhamid Elsayed, Mai Magdy Anwer, Abeer Mahmoud El-Bahy, Ahmed Salah","doi":"10.3389/fcimb.2025.1600225","DOIUrl":"10.3389/fcimb.2025.1600225","url":null,"abstract":"<p><strong>Introduction: </strong><i>Mycobacterium bovis</i> (<i>M. bovis</i>) causes significant financial harm to the cattle industry through decreased productivity and trade limitations, while also posing a risk to human health through zoonotic transmission, which is primarily from unpasteurized milk or close animal contact.</p><p><strong>Methods: </strong>Single intradermal tuberculin was used to test 2400 cases (1000 Holstein Friesian cattle and 1400 native breed buffaloes) during the national control program from Cairo, El-Buhaira, Dakahlia, Gharbia, Menoufia, and Sharkia districts located at the northern areas of Egypt. Tuberculin-positive cases were slaughtered and subjected to postmortem examination and isolation of <i>M. bovis</i> was performed. IS<i>6110</i> primer was used in PCR test to confirm the existence of genus mycobacterium and regions of difference-based differentiation was used to detect <i>M. bovis</i> on the species level, phenotypic and genotypic antimicrobial resistance, as well as mycobacterial interspersed repetitive unit-variable number tandem repeat analysis (MIRU-VNTR) were performed.</p><p><strong>Results: </strong>A total of 65 out of 2400 (2.7%) cases were single intradermal tuberculin test positive, 40 out of 65 (61.53%) were <i>M. bovis</i> positive on PCR, and the 40 isolates exhibited susceptibility to ethambutol, rifampicin, streptomycin, ciprofloxacin, levofloxacin, ofloxacin, and sparfloxacin. From them, 32 (80%) were susceptible to isoniazid, and 8 (20%) were resistant. These eight isolates contained three distinct <i>kat</i>G mutations at codons 315, 463, and 506 with rates of 2/8 (25%), 3/8 (37.5%), and 3/8 (37.5%), respectively each representing a unique, single-codon mutation. MIRU-VNTR analysis enabled the identification of 35 distinct genotypes, with genotypes 26, 27, and 28 showing high prevalence. The nine highly discriminatory loci MIRU10, QUB11b, MIRU26, QUB26, QUB4156, MIRU04 ETRD, ETRA, Mtub30, and Mtub39 with a discriminating index of 0.9676 were suitable for the preliminary genotyping of <i>M. bovis</i> isolates from animals. <i>M. bovis</i>, ID: 7540/01, Lineage: Bovis and ID: 951/01, Lineage: Bovis from Germany were the closest lineages to our genotypes using the MIRU-VNTR plus database.</p><p><strong>Conclusion: </strong><i>M. bovis</i> isolated from cattle and buffaloes of some Delta area districts expressed high diversity and some isolates showed resistance to isoniazid with <i>kat</i>G mutations. Continuous implementation of MIRU-VNTR analysis will help to trace the origin and similarities among animal and human isolates within the Delta area.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1600225"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring viral diversity in diarrheic porcine feces: a metagenomic analysis from an Indian swine farm.","authors":"Sushila Maan, Kanisht Batra, Jeyaprakash Rajendhran, Raison Joseph, Vikash K Singh, Deepika Chaudhary, Swati Sindhu, Vijay Kadian, Aman Kumar, Narender Singh Maan, Sunil Mor","doi":"10.3389/fcimb.2025.1653342","DOIUrl":"10.3389/fcimb.2025.1653342","url":null,"abstract":"<p><strong>Background: </strong>Pig husbandry is a vital sector in India, providing nutritional security and employment for marginalized communities. Pigs are advantageous due to high reproduction rates and fecundity, shorter generation intervals, and efficient feed conversion, requiring minimal housing. However, the swine industry encounters significant disease challenges, particularly viral gastroenteritis, which poses serious public health risks, especially in developing countries. Pigs serve as natural reservoirs and amplifiers for numerous viruses with zoonotic potential, making disease surveillance essential.</p><p><strong>Materials: </strong>In this study, we conducted a metagenomic analysis of 15 fecal samples from diarrheic pigs on a farm in India, marking the first exploration of the fecal virome diversity in this region. Our next-generation sequencing approach has enabled the unbiased detection of multiple viral agents in the porcine fecal samples, detecting both known and novel viral agents without prior target knowledge.</p><p><strong>Results: </strong>The key and novel viruses obtained in our study were porcine circovirus, porcine parvovirus 7, porcine mamastrovirus 3, porcine sapelovirus A, and porcine enterovirus G. This work resulted in the generation of full genomes for multiple porcine viruses, including <i>Circovirus, Enterovirus, Sapelovirus</i>, and <i>Mamastrovirus</i>, along with partial genomes of <i>Parvovirus, Picobirnavirus, Porcine stool-associated RNA virus</i> (Porcine Posavirus), <i>Kobuvirus</i>, and <i>Rotavirus</i>, all subjected to phylogenetic analysis.</p><p><strong>Conclusion: </strong>Our survey indicates frequent co-infections with diverse viruses, creating conducive environments for viral recombination and reassortment. Continuous surveillance of viral pathogens in animal populations is essential for understanding the dynamics of both known and novel viruses and for detecting emerging pathogens, along with their zoonotic and pathogenic potential.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1653342"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and functional characterization of a novel <i>Acinetobacter pittii</i> bacteriophage-encoded depolymerase.","authors":"Na Zhang, Wei Li, Xue Du, Danish Daniyal, Meng-Ai Feng, Jiaoyang Xu, Ziqin Yang, Hailin Jiang, Muhammad Sheraz, Honglan Huang, Santasree Banerjee, Hongyan Shi","doi":"10.3389/fcimb.2025.1608526","DOIUrl":"10.3389/fcimb.2025.1608526","url":null,"abstract":"<p><strong>Introduction: </strong><i>Acinetobacter pittii</i> is increasingly recognized as a significant cause of nosocomial infections. Bacteriophage-encoded depolymerases that degrade capsular polysaccharides (CPS)-a major virulence factor of <i>A. pittii</i>-represent promising therapeutic tools.</p><p><strong>Methods: </strong>This study identified and characterized a novel depolymerase, designated 31TSP, derived from the <i>A. pittii</i> bacteriophage 31Y. Its functional stability across various pH levels (5-11) and temperatures (4 °C to 121 °C) was assessed. The inhibitory effect of 31TSP on biofilm formation and its disruptive activity against preformed biofilms were evaluated using crystal violet staining, viable cell counts and scanning electron microscopy. Combinatorial treatments with 31TSP and ampicillin were conducted. Furthermore, the enzyme's stability under different ion concentrations (NaCl) and its ability to enhance serum bactericidal activity were tested under experimental conditions.</p><p><strong>Results: </strong>Characterization demonstrated that 31TSP exhibits a broad host range against <i>A. pittii</i>, <i>A. baumannii</i>, and <i>A. nosocomialis</i>. The enzyme degraded the CPS of host bacteria and displayed inhibition effects on sensitive hosts. 31TSP retained functional stability across a wide pH range (5-11) and temperatures from 4 °C to 121 °C. Its inhibitory effect on biofilm formation and disruptive activity against preformed biofilms were confirmed. Notably, combinatorial treatment with 31TSP and ampicillin significantly enhanced biofilm inhibition and disruption at 24 hours post-treatment. However, 31TSP did not maintain stability under different ion concentrations (NaCl) and could not enhance serum bactericidal activity under the experimental conditions.</p><p><strong>Discussion: </strong>These findings support the potential of 31TSP as an antibacterial agent against Acinetobacter infections. The observed synergy with conventional antibiotics, such as ampicillin, suggests a promising combinatorial strategy for future therapeutics targeting <i>Acinetobacter</i>. The enzyme's stability under extreme conditions of temperature and pH further underscores its therapeutic potential. However, its instability in varying ionic environments and lack of serum bactericidal enhancement highlight aspects requiring further investigation for clinical application.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1608526"},"PeriodicalIF":4.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics analysis of soluble secreted proteins of <i>Lutzomyia longipalpis</i> LL5 cells transfected with a dsRNA viral mimic: insights into cellular defense and repair signals.","authors":"Andrea Martins da Silva, Ilya Violeta Llanos Salamanca, Michel Batista, Fabricio Klerynton Marchini, Antonio Jorge Tempone, Erich Loza Telleria, Yara Maria Traub-Csekö","doi":"10.3389/fcimb.2025.1638505","DOIUrl":"10.3389/fcimb.2025.1638505","url":null,"abstract":"<p><p>Sand flies, which transmit diseases like leishmaniases, bartonellosis, and certain viruses, pose a significant public health threat. Our research focuses on the immune responses of <i>Lutzomyia longipalpis</i>, the primary vector for visceral leishmaniasis in the Americas. We use <i>L. longipalpis</i> LL5 cells as a model to study how sand flies respond to pathogens. These cells exhibit robust immune reactions, producing molecules mainly regulated by the Toll, IMD, Jak-STAT, and RNAi pathways. In previous studies, we detected a non-specific antiviral response in LL5 cells following double-stranded RNAs (dsRNAs) transfection. A previous complete secretome of these cells showed molecules resembling an interferon-like antiviral response when transfected with polyinosinic-polycytidylic acid (poly I:C), a synthetic dsRNA analog. In the current study, we analyzed soluble proteins secreted by LL5 cells after poly I:C transfection. Using comparative mass spectrometry, we examined protein composition of conditioned media depleted of exosomes at 24 h and 48 h. Most proteins uniquely expressed in the transfected groups had low abundance compared to the overall expressed proteins. Interactome prediction analysis revealed that at 24 h, the proteins uniquely found in the secretome of the transfected group were involved in RNA degradation and purine metabolism, while at 48 h they were linked to ribosomal proteins and signaling pathways such as Hedgehog, Transforming Growth Factor-beta (TGF-β), and Wingless/integrated (Wnt). We highlight increased abundance of the TGF-β-induced protein ig-h3 (24 h and 48 h), a Toll-like receptor 3 (48 h), and a hemocytin (48 h) in the secretion of transfected groups compared to the controls. We also performed an interaction analysis of proteins more secreted by the treated group at 24 h and 48 h. Unlike the interactome of uniquely identified proteins, few interactions were observed at 24 h, with a predominance of extracellular matrix and cell adhesion proteins. The set of proteins more secreted at 48 h presented more interactions than at 24 h, with emphasis on catabolic processes, including RNA degradation. These findings indicate that poly I:C transfection in LL5 cells induces the secretion of proteins involved in cellular defense and repair, revealing molecules involved in the LL5 non-specific antiviral response.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1638505"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryptococcal infection: host immunity, immune evasion and emerging immunotherapeutic strategies.","authors":"Fei Li, Xinxin Yu, Miao Li, Xiaoyu Ning, Kaijian Zhou","doi":"10.3389/fcimb.2025.1671873","DOIUrl":"10.3389/fcimb.2025.1671873","url":null,"abstract":"<p><p>Cryptococcal infection is a typical opportunistic infection that significantly endangers human health, particularly to immunocompromised populations. As the top priority fungal pathogen listed by the World Health Organization, conventional antifungal drugs for cryptococcal infection are often ineffective and fail to completely eradicate the pathogen. One of the key factors underlying the treatment failure is the sophisticated immune escape strategies employed by <i>Cryptococcus</i>, which constitutes a major clinical challenge. Overcoming immune escape is key to improving therapeutic efficacy. Therefore, exploring new therapeutic methods, especially immunotherapy, is of paramount importance in combating the escape mechanisms and boosting the host's defense capabilities. In this review, we focus on the host's pattern recognition receptors, the innate and adaptive immune responses to the <i>Cryptococcus</i> infection, the immune escape tricks of <i>Cryptococcus</i>, and the prospects for immunotherapy, providing new insights for developing the anti-<i>Cryptococcus</i> immunotherapeutic strategies for the immunocompromised populations.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1671873"},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}