Examinando por Autor "Ramos-Tapia, Ignacio"
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Ítem Bacterial small RNAs may mediate immune response differences seen in respiratory syncytial virus versus rhinovirus bronchiolitis(Frontiers Media SA, 2024) Krohmaly, Kylie I.; Perez-Losada, Marcos; Ramos-Tapia, Ignacio; Zhu, Zhaozhong; Hasegawa, Kohei; Camargo Jr, Carlos A.; Harmon, Brennan; Espinola, Janice A.; Reck Cechinel, Laura; Batabyal, Rachael; Freishtat, Robert J.; Hahn, AndreaBronchiolitis, a viral lower respiratory infection, is the leading cause of infant hospitalization, which is associated with an increased risk for developing asthma later in life. Bronchiolitis can be caused by several respiratory viruses, such as respiratory syncytial virus (RSV), rhinovirus (RV), and others. It can also be caused by a solo infection (e.g., RSV- or RV-only bronchiolitis) or co-infection with two or more viruses. Studies have shown viral etiology-related differences between RSV- and RV-only bronchiolitis in the immune response, human microRNA (miRNA) profiles, and dominance of certain airway microbiome constituents. Here, we identified bacterial small RNAs (sRNAs), the prokaryotic equivalent to eukaryotic miRNAs, that differ between infants of the 35th Multicenter Airway Research Collaboration (MARC-35) cohort with RSV- versus RV-only bronchiolitis. We first derived reference sRNA datasets from cultures of four bacteria known to be associated with bronchiolitis (i.e., Haemophilus influenzae, Moraxella catarrhalis, Moraxella nonliquefaciens, and Streptococcus pneumoniae). Using these reference sRNA datasets, we found several sRNAs associated with RSV- and RV-only bronchiolitis in our human nasal RNA-Seq MARC-35 data. We also determined potential human transcript targets of the bacterial sRNAs and compared expression of the sRNAs between RSV- and RV-only cases. sRNAs are known to downregulate their mRNA target, we found that, compared to those associated with RV-only bronchiolitis, sRNAs associated with RSV-only bronchiolitis may relatively activate the IL-6 and IL-8 pathways and relatively inhibit the IL-17A pathway. These data support that bacteria may be contributing to inflammation differences seen in RSV- and RV-only bronchiolitis, and for the first time indicate that the potential mechanism in doing so may be through bacterial sRNAs.Ítem Characterization of the upper respiratory tract microbiota in Chilean asthmatic children reveals compositional, functional, and structural differences(Frontiers Media S.A., 2023-07) Ramos-Tapia, Ignacio; Reynaldos-Grandón, Katiuska L.; Pérez-Losada, Marcos; Castro-Nallar, EduardoAround 155 million people worldwide suffer from asthma. In Chile, the prevalence of this disease in children is around 15% and has a high impact in the health system. Studies suggest that asthma is caused by multiple factors, including host genetics, antibiotic use, and the development of the airway microbiota. Here, we used 16S rRNA high-throughput sequencing to characterize the nasal and oral mucosae of 63 asthmatic and 89 healthy children (152 samples) from Santiago, Chile. We found that the nasal mucosa was dominated by a high abundance of Moraxella, Dolosigranulum, Haemophilus, Corynebacterium, Streptococcus, and Staphylococcus. In turn, the oral mucosa was characterized by a high abundance of Streptococcus, Haemophilus, Gemella, Veillonella, Neisseria, and Porphyromonas. Our results showed significantly (P < 0.001) lower alpha diversity and an over-abundance of Streptococcus (P < 0.01) in nasal samples from asthmatics compared to samples from healthy subjects. Community structure, as revealed by co-occurrence networks, showed different microbial interactions in asthmatic and healthy subjects, particularly in the nasal microbiota. The networks revealed keystone genera in each body site, including Prevotella, Leptotrichia, and Porphyromonas in the nasal microbiota, and Streptococcus, Granulicatella, and Veillonella in the oral microbiota. We also detected 51 functional pathways differentially abundant on the nasal mucosa of asthmatic subjects, although only 13 pathways were overrepresented in the asthmatic subjects (P < 0.05). We did not find any significant differences in microbial taxonomic (composition and structure) and functional diversity between the oral mucosa of asthmatic and healthy subjects. This study explores for the first time the relationships between the upper respiratory airways bacteriome and asthma in Chile. It demonstrates that the nasal cavity of children from Santiago harbors unique bacterial communities and identifies potential taxonomic and functional biomarkers of pediatric asthma. 2023 Ramos-Tapia, Reynaldos-Grandón, Pérez-Losada and Castro-Nallar.Ítem Human metapneumovirus respiratory infection affects both innate and adaptive intestinal immunity(Frontiers Media SA, 2024) Sepúlveda-Alfaro, Javiera; Catalán, Eduardo A.; Vallejos, Omar P.; Ramos-Tapia, Ignacio; Madrid-Muñoz, Cristóbal; Mendoza-León, María J.; Suazo, Isidora D.; Rivera-Asin, Elizabeth; Silva, Pedro H.; Alvarez-Mardones, Oscar; Castillo-Godoy, Daniela P.; Riedel, Claudia A.; Schinnerling, Katina; Ugalde, Juan A.; Soto, Jorge A.; Bueno, Susan M.; Kalergis, Alexis M.; Melo-Gonzalez, FelipeIntroduction: Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied. Methods: Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group. Results: We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8+ T cells and memory precursor effector CD8+ T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA+ plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in β-diversity and relative abundance at the genus level. Discussion: To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.Ítem Immunoglobulin E-virus phenotypes of infant bronchiolitis and risk of childhood asthma(Frontiers Media S.A., 2023) Shibata, Ryohei; Zhu, Zhaozhong; Ooka, Tadao; Freishtat, Robert J.; Mansbach, Jonathan M.; Pérez-Losada, Marcos; Ramos-Tapia, Ignacio; Teach, Stephen; Camargo, Carlos A.; Hasegawa, KoheiBackground: Bronchiolitis is the leading cause of infant hospitalization in U.S. and is associated with increased risk for childhood asthma. Immunoglobulin E (IgE) not only plays major roles in antiviral immune responses and atopic predisposition, but also offers a potential therapeutic target. Objective: We aimed to identify phenotypes of infant bronchiolitis by using total IgE (tIgE) and virus data, to determine their association with asthma development, and examine their biological characteristics. Methods: In a multicenter prospective cohort study of 1,016 infants (age <1 year) hospitalized for bronchiolitis, we applied clustering approaches to identify phenotypes by integrating tIgE and virus (respiratory syncytial virus [RSV], rhinovirus [RV]) data at hospitalization. We examined their longitudinal association with the risk of developing asthma by age 6 years and investigated their biological characteristics by integrating the upper airway mRNA and microRNA data in a subset (n=182). Results: In infants hospitalized for bronchiolitis, we identified 4 phenotypes: 1) tIgElowvirusRSV-high, 2) tIgElowvirusRSV-low/RV, 3) tIgEhighvirusRSV-high, and 4) tIgEhighvirusRSV-low/RV phenotypes. Compared to phenotype 1 infants (resembling “classic” bronchiolitis), phenotype 4 infants (tIgEhighvirusRSV-low/RV) had a significantly higher risk for developing asthma (19% vs. 43%; adjOR, 2.93; 95% CI, 1.02–8.43; P=.046). Phenotypes 3 and 4 (tIgEhigh) had depleted type I interferon and enriched antigen presentation pathways; phenotype 4 also had depleted airway epithelium structure pathways. Conclusions: In this multicenter cohort, tIgE-virus clustering identified distinct phenotypes of infant bronchiolitis with differential risks of asthma development and unique biological characteristics. Copyright © 2023 Shibata, Zhu, Ooka, Freishtat, Mansbach, Pérez-Losada, Ramos-Tapia, Teach, Camargo and Hasegawa.