Claudia Fançony, Elsa Fortes-Gabriel, Félix Zage, Evangelia Alexiou, Ioanna Broumou, Leyre Pernaute-Lau, Jorge Panzo, Esperança J António, Mario S Cristovão, José M Domingos, Estevão Sassoma, Fernando Kuatoko, Edite V N Rosario, António Martins, Anna Färnert, Luis Bernardino, Tais N de Sousa, José Pedro Gil
{"title":"Artemether-Lumefantrine Treatment Selects Plasmodium falciparum Multidrug Resistance 1 (pfmdr1) Increased Copy Number Among African Malaria Infections.","authors":"Claudia Fançony, Elsa Fortes-Gabriel, Félix Zage, Evangelia Alexiou, Ioanna Broumou, Leyre Pernaute-Lau, Jorge Panzo, Esperança J António, Mario S Cristovão, José M Domingos, Estevão Sassoma, Fernando Kuatoko, Edite V N Rosario, António Martins, Anna Färnert, Luis Bernardino, Tais N de Sousa, José Pedro Gil","doi":"10.1093/infdis/jiaf155","DOIUrl":"10.1093/infdis/jiaf155","url":null,"abstract":"<p><strong>Background: </strong>Decreased efficacy of artemether-lumefantrine, the globally most used antimalarial, has recently emerged in Africa.</p><p><strong>Methods: </strong>An efficacy trial was carried out based on directly observed artemether-lumefantrine therapy at Bengo, Northern Angola. One-hundred Plasmodium falciparum uncomplicated malaria patients (2-10 years old) were enrolled, hospitalized for the treatment period, and followed up for 42 days. Polymerase chain reaction (PCR) correction was performed with pfmsp1/2 plus glurp, with analysis considering 2 or 3 coincident markers. Infections were tested by quantitative PCR (qPCR) for pfmdr1 copy number (pfmdr1×N), a potential P. falciparum marker of lumefantrine resistance previously identified in the region. In vitro clone mixtures were built and used to determine the relation between qPCR copy number scores and actual intrainfection quantitative fractions of pfmdr1×N.</p><p><strong>Results: </strong>We observed a significant posttreatment selection of gene amplification, suggesting a role in the parasite in vivo response to this drug. pfmdr1×2 qPCR scores of 1.3, 1.4, and 1.5 were determined to correspond to 15%, 25%, and 35% intrainfection rates. Patients carrying infections with a score ≥1.4 at baseline were linked to decreased artemether-lumefantrine day 42 efficacy (79% vs 97% single-copy pfmdr1). All infections were pfmdr1 N86 carriers and no pfk13 mutations were found.</p><p><strong>Conclusions: </strong>Our study suggests pfmdr1×N as a marker of P. falciparum in vivo response to lumefantrine in Africa, while indicating patients carrying infections with a pretreatment pfmdr1×N score ≥1.4 before treatment are a group experiencing decreased artemether-lumefantrine performance.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1119-e1128"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732975","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}
Tiina Holster, Päivi Joki-Korpela, Hong Yu, Robert C Brunham, Aila Tiitinen, Jorma Paavonen, Mirja Puolakkainen
{"title":"Serum IgG1 and IgG3 Antibody Responses to Chlamydia trachomatis Pgp3 and Hsp60 in Tubal Factor Infertility.","authors":"Tiina Holster, Päivi Joki-Korpela, Hong Yu, Robert C Brunham, Aila Tiitinen, Jorma Paavonen, Mirja Puolakkainen","doi":"10.1093/infdis/jiaf092","DOIUrl":"10.1093/infdis/jiaf092","url":null,"abstract":"<p><strong>Background: </strong>Our goal was to investigate IgG1 and IgG3 antibody responses to Chlamydia trachomatis proteins Pgp3 and Hsp60 in women with tubal factor infertility (TFI). Our goal was to determine the role of these biomarkers in the diagnosis of C. trachomatis-associated TFI, and assess their sensitivity and specificity for detecting tubal pathology.</p><p><strong>Methods: </strong>Serum samples were collected from 258 subfertile women, and 34 women positive for C. trachomatis by nucleic acid amplification test (NAAT). IgG1 and IgG3 antibodies to Pgp3 and Hsp60 were measured using enzyme immune assays.</p><p><strong>Results: </strong>Pgp3 IgG1 antibodies were detected in 68.2% of TFI cases and 31.8% of controls (non-TFI), while Hsp60 IgG1 antibodies were found in 36.4% of TFI cases. Pgp3 IgG1 had the highest sensitivity for TFI (68.2%; 95% confidence interval [CI], 45.1%-86.1%), while Hsp60 IgG3 was the most specific (93.6%; 95% CI, 89.7-96.4). Antibody levels increased with tubal damage severity. Among the 34 NAAT-positive women, 78.8% were positive for Pgp3 IgG1.</p><p><strong>Conclusions: </strong>Pgp3 IgG1 antibody was a sensitive marker for detecting C. trachomatis-related TFI, while Hsp60 IgG3 antibody was highly specific. These findings suggest that Pgp3 and Hsp60 antibodies and antibody subclass testing may be useful diagnostic tools for assessing TFI.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1057-e1064"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469758","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":"Oops, the Microbes Did It Again: Gut Dysbiosis Precedes Late-Onset Meningitis.","authors":"Samantha A Whiteside, Audrey R Odom John","doi":"10.1093/infdis/jiae266","DOIUrl":"10.1093/infdis/jiae266","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1349-1352"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mar Masiá, José A García, Javier García-Abellán, Sergio Padilla, Marta Fernández-González, Vanesa Agulló, Maria José Gosalbes, Sonia Ruíz-Pérez, Paula Mascarell, Angela Botella, Félix Gutiérrez
{"title":"Distinct Gut Microbiota Signatures Associated With Progression of Atherosclerosis in People Living With Human Immunodeficiency Virus.","authors":"Mar Masiá, José A García, Javier García-Abellán, Sergio Padilla, Marta Fernández-González, Vanesa Agulló, Maria José Gosalbes, Sonia Ruíz-Pérez, Paula Mascarell, Angela Botella, Félix Gutiérrez","doi":"10.1093/infdis/jiae243","DOIUrl":"10.1093/infdis/jiae243","url":null,"abstract":"<p><strong>Background: </strong>The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with human immunodeficiency virus (PWH) remains unknown.</p><p><strong>Methods: </strong>A 96-week, prospective, longitudinal study was performed in virologically suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline and at 48- and 96-week visits. cIMT progression was defined as an increase of >10% and/or detection of new carotid plaque. To profile the gut microbiome, amplification and sequencing of 16S ribosomal RNA (V3-V4 variable regions) were carried out, following the Illumina protocol. Sequencing was performed using the MiSeq platform.</p><p><strong>Results: </strong>At the baseline, 48-week, and 96-week visits, 191, 190, and 167 patients, respectively, had fecal samples available for microbiome analysis. Eighty-seven participants (43%) showed atherosclerosis progression, and 54 (26.7%) presented with new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups, defined by cIMT progression. β-Diversity, determined through principal coordinate analysis, showed that the groups exhibited distinct microbial profiles (P = .03; permutational multivariate analysis of variance). Longitudinal analysis with Analysis of Compositions of Microbiomes with Bias Correction 2, adjusted for traditional cardiovascular risk factors, status as men who have sex with men, and nadir CD4 count, revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus 2, while nonprogression was consistently associated with Prevotella 7.</p><p><strong>Conclusions: </strong>Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1371-1381"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María José Forcadell-Peris, Ángel Vila-Córcoles, Cinta de Diego-Cabanes, Verònica Torras Vives, Olga Ochoa-Gondar, Eva M Satué-Gracia
{"title":"Evaluating Sex Differences in Pneumococcal Disease Burden and Vaccination Effectiveness in Adults: A Population-Based Study.","authors":"María José Forcadell-Peris, Ángel Vila-Córcoles, Cinta de Diego-Cabanes, Verònica Torras Vives, Olga Ochoa-Gondar, Eva M Satué-Gracia","doi":"10.1093/infdis/jiae624","DOIUrl":"10.1093/infdis/jiae624","url":null,"abstract":"<p><strong>Background: </strong>Information concerning sex differences in pneumococcal vaccine effectiveness in adults is scarce. The main aim of this study is to compare the differences in clinical effectiveness of pneumococcal vaccination between male and female.</p><p><strong>Methods: </strong>This was a population-based cohort study involving 1 108 634 women and 951 011 men aged ≥50 years in Catalonia, Spain. Baseline characteristics of cohort members were established according to Institutional Research Database and pneumococcal disease-related hospitalizations (PDRH) captured from hospital discharge codes from 68 reference Catalonian hospitals during 2017-2018. Cox regression models were used to estimate PPsV23/PCV13 effectiveness against PDRH by sex.</p><p><strong>Results: </strong>Across the 2-year follow-up, 4302 PDRH cases (1878 women, 2424 men) were observed, with incidences of 169.4/100 000 and 254.9/100 000 for women and men, respectively. Among women, neither PPsV23 (hazard ratio [HR], 1.04; 95% confidence interval [CI], .92-1.18; P = .540) or PCV13 (HR, 1.24; 95% CI, .91-1.70; P = .171) altered PDRH risk. Among men, PCV13 was associated with significantly increased risk of PDRH (HR, 1.57; 95% CI, 1.07-2.31; P = .021) whereas PPsV23 did not significantly alter this risk (HR, 0.89; 95% CI, .72-1.10; P = .275). No reduced risk of death following PDRH was observed in vaccinated women or men. However, regarding all-cause death, PPsV23 showed slight reduction in risk for women (HR, 0.94; 95% CI, .92-.97; P < .001).</p><p><strong>Conclusions: </strong>PPsV23/PCV13 vaccinations have not proven effective for either sex in preventing PDRH. PPsV23 appears associated with slight reduction risk of all-cause death in women, which could be related to better or longer-lasting vaccination effects in women compared to men.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1455-1464"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nina M Frerichs, Nancy Deianova, Sofia El Manouni El Hassani, Animesh Acharjee, Mohammed Nabil Quraishi, Willem P de Boode, Veerle Cossey, Christian V Hulzebos, Anton H van Kaam, Boris W Kramer, Esther d'Haens, Wouter J de Jonge, Daniel C Vijlbrief, Mirjam M van Weissenbruch, Emma Daulton, Alfian N Wicaksono, James A Covington, Marc A Benninga, Nanne K H de Boer, Johannes B van Goudoever, Hendrik J Niemarkt, Tim G J de Meij
{"title":"Fecal Microbiota and Volatile Metabolome Pattern Alterations Precede Late-Onset Meningitis in Preterm Neonates.","authors":"Nina M Frerichs, Nancy Deianova, Sofia El Manouni El Hassani, Animesh Acharjee, Mohammed Nabil Quraishi, Willem P de Boode, Veerle Cossey, Christian V Hulzebos, Anton H van Kaam, Boris W Kramer, Esther d'Haens, Wouter J de Jonge, Daniel C Vijlbrief, Mirjam M van Weissenbruch, Emma Daulton, Alfian N Wicaksono, James A Covington, Marc A Benninga, Nanne K H de Boer, Johannes B van Goudoever, Hendrik J Niemarkt, Tim G J de Meij","doi":"10.1093/infdis/jiae265","DOIUrl":"10.1093/infdis/jiae265","url":null,"abstract":"<p><strong>Background: </strong>The fecal microbiota and metabolome are hypothesized to be altered before late-onset neonatal meningitis (LOM), analogous to late-onset sepsis (LOS). The present study aimed to identify fecal microbiota composition and volatile metabolomics preceding LOM.</p><p><strong>Methods: </strong>Cases and gestational age-matched controls were selected from a prospective, longitudinal preterm cohort study (born <30 weeks' gestation) at 9 neonatal intensive care units. The microbial composition (16S rRNA sequencing) and volatile metabolome (gas chromatography-ion mobility spectrometry [GC-IMS] and GC-time-of-flight-mass spectrometry [GC-TOF-MS]) were analyzed in fecal samples 1-10 days pre-LOM.</p><p><strong>Results: </strong>Of 1397 included infants, 21 were diagnosed with LOM (1.5%), and 19 with concomitant LOS (90%). Random forest classification and MaAsLin2 analysis found similar microbiota features contribute to the discrimination of fecal pre-LOM samples versus controls. A random forest model based on 6 microbiota features accurately predicted LOM 1-3 days before diagnosis with an area under the curve (AUC) of 0.88 (n = 147). Pattern recognition analysis by GC-IMS revealed an AUC of 0.70-0.76 (P < .05) in the 3 days pre-LOM (n = 92). No single discriminative metabolites were identified by GC-TOF-MS (n = 66).</p><p><strong>Conclusions: </strong>Infants with LOM could be accurately discriminated from controls based on preclinical microbiota composition, while alterations in the volatile metabolome were moderately associated with preclinical LOM.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1382-1391"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088908","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}
Tobias R Kollmann, Nelly Amenyogbe, Frederik Schaltz-Buchholzer, Ole Bæk, James Campbell, David J Lynn, Anita J Campbell, Peter Aaby, Christine Stabell Benn, Mihai G Netea, Maziar Divangahi
{"title":"Is Systemic Dissemination of BCG Following Neonatal Vaccination Required for Protection Against Mycobacterium tuberculosis?","authors":"Tobias R Kollmann, Nelly Amenyogbe, Frederik Schaltz-Buchholzer, Ole Bæk, James Campbell, David J Lynn, Anita J Campbell, Peter Aaby, Christine Stabell Benn, Mihai G Netea, Maziar Divangahi","doi":"10.1093/infdis/jiaf051","DOIUrl":"10.1093/infdis/jiaf051","url":null,"abstract":"<p><p>Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and is a leading cause of death. BCG is the only licensed TB vaccine. Preclinical studies have shown that in adults, intravenous administration of BCG improves protection against TB. We hypothesize that intradermal administration of BCG to the human newborn leads to low-grade BCG bacteremia and that this systemic dissemination improves protection against Mtb infection. This hypothesis is based on supporting observations including animal and human studies. It is a testable hypothesis and offers to deliver immediately actionable insight to advance the global efforts against TB.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1019-e1021"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366421","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}
Esperanza Muñoz-Muela, Marta Mejías-Trueba, Ana Serna-Gallego, Abraham Saborido-Alconchel, Susana Fernández-Pérez, Marta Herrero, Cesar Sotomayor, Alicia Gutiérrez-Valencia, María Trujillo-Rodríguez, Luis F López-Cortés
{"title":"Mitochondrial Disorders After 12 Months of Human Immunodeficiency Virus Type 1 Preexposure Prophylaxis Based on Tenofovir Disoproxil Fumarate Plus Emtricitabine in Healthy Adults.","authors":"Esperanza Muñoz-Muela, Marta Mejías-Trueba, Ana Serna-Gallego, Abraham Saborido-Alconchel, Susana Fernández-Pérez, Marta Herrero, Cesar Sotomayor, Alicia Gutiérrez-Valencia, María Trujillo-Rodríguez, Luis F López-Cortés","doi":"10.1093/infdis/jiaf156","DOIUrl":"10.1093/infdis/jiaf156","url":null,"abstract":"<p><strong>Background: </strong>New nucleos(t)ide reverse transcriptase inhibitors are considerably less toxic than their predecessors, but they may not be entirely devoid of toxicity. However, their effect in healthy adults remains unknown. We aimed to analyze the impact of tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC)-based preexposure prophylaxis (PrEP) on mitochondria of subjects at high risk of human immunodeficiency virus type 1 infection.</p><p><strong>Methods: </strong>This was an observational, prospective study of 59 healthy adults enrolled in the PrEP program at Virgen del Rocío University Hospital. Mitochondrial DNA and common deletion 4977 were measured using digital droplet polymerase chain reaction. Mitochondrial density, membrane potential, oxidative stress, metabolic profile, and morphology were assessed by flow cytometry, real-time cellular bioenergetics measurements, and transmission electron microscopy, respectively, at baseline and after 12 months. Values were compared by the Wilcoxon test, and correlations between variables were assessed using the Spearman rank correlation coefficient (ρ).</p><p><strong>Results: </strong>Our results showed that after 12 months, TDF/FTC induced a mitochondrial oxidative stress increase in myeloid and lymphoid populations. Mitochondrial density decreased in CD8+ T cells and natural killer cells, while mitochondrial membrane potential was augmented in all lymphoid populations. Cell bioenergetic health was compromised, evidenced by reduced oxygen consumption rate, declined adenosine triphosphate production, and impaired response capacity to an energetic demand. Changes in the shape, membrane integrity, cristae structure, size, and distribution of the mitochondria throughout the cytoplasm were also observed. All participants experienced alterations in 1 or more measured parameters.</p><p><strong>Conclusions: </strong>TDF/FTC-based PrEP induces mitochondrial toxicity in healthy subjects after 12 months of treatment, negatively affecting mitochondrial function and morphology.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1430-1439"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Archana Koirala, Katherine Smith, Philip N Britton, Annaleise R Howard-Jones, Vitali Sintchenko, Ellen J Donnan, Evan Ulbricht, Elena Martinez, Reta Toma, Ben J Marais
{"title":"Protracted Tuberculosis Outbreak in a Pasifika Diaspora in Western Sydney, Australia: The Importance of Community Engagement.","authors":"Archana Koirala, Katherine Smith, Philip N Britton, Annaleise R Howard-Jones, Vitali Sintchenko, Ellen J Donnan, Evan Ulbricht, Elena Martinez, Reta Toma, Ben J Marais","doi":"10.1093/infdis/jiae619","DOIUrl":"10.1093/infdis/jiae619","url":null,"abstract":"<p><p>A prolonged tuberculosis outbreak, linked by whole-genome sequencing, occurred in a Pasifika extended family over 10 years (2013-2022) in Sydney, Australia. Despite Australia's low tuberculosis incidence, social and cultural complexities, and coronavirus disease 2019 (COVID-19) disruptions exacerbated transmission. Control required culturally sensitive, family-centered care and robust health system engagement.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1532-1535"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francisco Callejas-Hernández, Alfonso Herreros-Cabello, Cristina Poveda, María C Maza, José Francisco Mares, Diana K Santos-Peñaloza, Manuel Fresno, Núria Gironès
{"title":"RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis.","authors":"Francisco Callejas-Hernández, Alfonso Herreros-Cabello, Cristina Poveda, María C Maza, José Francisco Mares, Diana K Santos-Peñaloza, Manuel Fresno, Núria Gironès","doi":"10.1093/infdis/jiaf074","DOIUrl":"10.1093/infdis/jiaf074","url":null,"abstract":"<p><strong>Background: </strong>Trypanosoma cruzi is a protozoan parasite responsible for Chagas disease, affecting millions globally. This parasite infects mammalian host cells, particularly macrophages. The interaction between T. cruzi and macrophages involves intricate signaling pathways mediated by pattern recognition receptors, which lead to the production of immune mediators, that are parasite-strain dependent and not completely understood.</p><p><strong>Methods: </strong>We conducted an unbiased transcriptomic analysis of the immune response in mouse macrophages 24 hours postinfection with the Y strain of T. cruzi using RNA-Seq and validated and compared the results using quantitative RT-PCR in macrophages infected with the Y and the VFRA T. cruzi strains.</p><p><strong>Results: </strong>Bioinformatics analysis of the transcriptomics results evidenced a key role of Toll-like receptor 2 (Tlr2) and Tlr7 in the immune response against the parasite that was parasite-dependent. Tlr2 signaling was more activated with the VFRA strain and Tlr7 with the Y strain. Gene ontology analyses predicted a blockage in iron transport mediated by clathrin and the modulation of the extracellular matrix biosynthesis, which were validated by RT-qPCR. Infection with the VFRA strain provoked the inhibition of ferritin, which correlated with parasite proliferation.</p><p><strong>Conclusions: </strong>Our study recapitulates knowledge on the response of macrophages and provides insights into the importance of TLR2 and TLR7, iron metabolism, and extracellular matrix in the infected macrophage, which help the understanding of molecular mechanisms underlying T. cruzi infection in macrophages with strains with different virulence. These findings are crucial for identifying novel therapeutic targets and advancing strategies to combat Chagas disease.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1102-e1113"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416079","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}