Browsing by Author "Naves Pichuante, Rodrigo Antonio"

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    Differential levels of anti-Mycobacterium tuberculosis-specific IgAs in saliva of household contacts with latent tuberculosis infection
    (FRONTIERS MEDIA SA, 2023) Ruiz-Tagle Seguel, Cinthya Grace; Naves Pichuante, Rodrigo Antonio; Garcia Canete, Patricia Del Carmen; Guenther, Anna; Schneiderhan-Marra, Nicole; Balcells Marty, Maria Elvira
    Introduction: Mucosal immunity is strongly elicited in early stages of many respiratory and enteric infections; however, its role in tuberculosis pathogenesis has been scarcely explored. We aimed to investigate Mycobacterium tuberculosis (Mtb) specific IgA levels in saliva in different stages of latent Tuberculosis Infection (TBI).Methodology: A multiplex bead-based Luminex immunoassay was developed to detect specific IgA against 12 highly immunogenic Mtb antigens. A prospective cohort of household contacts (>14 years) of pulmonary TB cases was established in Santiago, Chile. Contacts were classified as Mtb-infected or not depending on serial interferon-gamma release assay results. Saliva samples were collected and tested at baseline and at a 12-week follow-up.Results: Mtb-specific IgA was detectable at all visits in all participants (n = 168), including the "non-Mtb infected" (n = 64). Significantly higher median levels of IgA were found in the "Mtb infected" compared to the uninfected for anti-lipoarabinomannan (LAM) (110 vs. 84.8 arbitrary units (AU), p < 0.001), anti-PstS1 (117 vs. 83 AU, p < 0.001), anti-Cell Membrane Fraction (CMF) (140 vs. 103 AU, p < 0.001) and anti-Culture Filtrate Proteins (CFP) (median 125 vs. 96 AU, p < 0.001), respectively. Nonetheless, the discriminatory performance of these specific mucosal IgA for TBI diagnosis was low.Conclusion: Saliva holds Mtb-specific IgA against several antigens with increased levels for anti-LAM, anti-PstS1, anti-CMF and anti-CFP found in household contacts with an established TBI. The role of these mucosal antibodies in TB pathogenesis, and their kinetics in different stages of Mtb infection merits further exploring.
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    Reduced microbial diversity of the nasopharyngeal microbiome in household contacts with latent tuberculosis infection
    (NATURE PORTFOLIO, 2023) Ruiz-Tagle Seguel, Cinthya Grace; Ugalde, Juan A.; Naves Pichuante, Rodrigo Antonio; Araos, Rafael; Garcia Canete, Patricia Del Carmen; Balcells Marty, Maria Elvira
    The upper respiratory tract is an obliged pathway for respiratory pathogens and a healthy microbiota may support the host's mucosal immunity preventing infection. We analyzed the nasopharyngeal microbiome in tuberculosis household contacts (HHCs) and its association with latent tuberculosis infection (TBI). A prospective cohort of HHCs was established and latent TBI status was assessed by serial interferon-& gamma; release assay (IGRA). Nasopharyngeal swabs collected at baseline were processed for 16S rRNA gene sequencing. The 82 participants included in the analysis were classified as: (a) non-TBI [IGRA negative at baseline and follow-up, no active TB (n = 31)], (b) pre-TBI [IGRA negative at baseline but converted to IGRA positive or developed active TB at follow-up (n = 16)], and (c) TBI [IGRA positive at enrollment (n = 35)]. Predominant phyla were Actinobacteriota, Proteobacteria, Firmicutes and Bacteroidota. TBI group had a lower alpha diversity compared to non-TBI (p(adj) = 0.04) and pre-TBI (p(adj) = 0.04). Only TBI and non-TBI had beta diversity differences (p(adj) = 0.035). Core microbiomes' had unique genera, and genus showed differential abundance among groups. HHCs with established latent TBI showed reduced nasopharyngeal microbial diversity with distinctive taxonomical composition. Whether a pre-existing microbiome feature favors, are a consequence, or protects against Mycobacterium tuberculosis needs further investigation.
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    Vitamin D and cathelicidin levels and susceptibility to Mycobacterium tuberculosis infection acquisition in household contactsNiveles de vitamina D y catelicidina y susceptibilidad a la infección por Mycobacterium tuberculosis en contactos intradomiciliarios
    (Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica, 2022) Ruiz-tagle Seguel Cinthya Grace; Romero, Francisco; Naves Pichuante, Rodrigo Antonio; Balcells Marty, Maria Elvira
    Introduction: Vitamin D deficiency has been proposed to confer susceptibility to acquiring tuberculosis infection by impairing the innate immune response. Methods: In an exploratory study, we examined whether the levels of 25-hydroxyvitamin D3 (25(OH)D3) in serum, and cathelicidin – an antimicrobial peptide-induced under calcitriol – in the nasal fluid, would associate with the risk of acquiring tuberculosis infection. Results: Within a prospective cohort of 231 tuberculosis household contacts tested with repeated interferon-gamma release assays, we serially analyzed all the uninfected contacts acquiring tuberculosis infection at follow-up (“converters”, n = 18), and an age and sex-matched control group of contacts not acquiring tuberculosis infection (“non-converters”, n = 36). The median levels of serum 25(OH)D3 did not differ between convertors and non-converters at baseline (14.9 vs. 13.2 ng/ml, p = 0.41), nor at follow-up (19.0 vs 18.6 ng/ml, p = 0.83). Similarly, cathelicidin levels did not differ between both groups. Conclusion: These data argue against a major role for hypovitaminosis D in tuberculosis infection susceptibility. © 2022 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica