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2.
Nat Immunol ; 25(8): 1411-1421, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38997431

ABSTRACT

A subset of individuals exposed to Mycobacterium tuberculosis (Mtb) that we refer to as 'resisters' (RSTR) show evidence of IFN-γ- T cell responses to Mtb-specific antigens despite serially negative results on clinical testing. Here we found that Mtb-specific T cells in RSTR were clonally expanded, confirming the priming of adaptive immune responses following Mtb exposure. RSTR CD4+ T cells showed enrichment of TH17 and regulatory T cell-like functional programs compared to Mtb-specific T cells from individuals with latent Mtb infection. Using public datasets, we showed that these TH17 cell-like functional programs were associated with lack of progression to active tuberculosis among South African adolescents with latent Mtb infection and with bacterial control in nonhuman primates. Our findings suggested that RSTR may successfully control Mtb following exposure and immune priming and established a set of T cell biomarkers to facilitate further study of this clinical phenotype.


Subject(s)
CD4-Positive T-Lymphocytes , Mycobacterium tuberculosis , Tuberculosis , Mycobacterium tuberculosis/immunology , Humans , Animals , Adolescent , Tuberculosis/immunology , Tuberculosis/microbiology , CD4-Positive T-Lymphocytes/immunology , Th17 Cells/immunology , Female , Macaca mulatta , Male , Phenotype , Interferon-gamma/metabolism , Interferon-gamma/immunology , Antigens, Bacterial/immunology , Latent Tuberculosis/immunology , Latent Tuberculosis/microbiology , South Africa , Young Adult , T-Lymphocytes, Regulatory/immunology , Adult
3.
Nat Med ; 29(1): 258-269, 2023 01.
Article in English | MEDLINE | ID: mdl-36604540

ABSTRACT

Antigen-specific, MHC-restricted αß T cells are necessary for protective immunity against Mycobacterium tuberculosis, but the ability to broadly study these responses has been limited. In the present study, we used single-cell and bulk T cell receptor (TCR) sequencing and the GLIPH2 algorithm to analyze M. tuberculosis-specific sequences in two longitudinal cohorts, comprising 166 individuals with M. tuberculosis infection who progressed to either tuberculosis (n = 48) or controlled infection (n = 118). We found 24 T cell groups with similar TCR-ß sequences, predicted by GLIPH2 to have common TCR specificities, which were associated with control of infection (n = 17), and others that were associated with progression to disease (n = 7). Using a genome-wide M. tuberculosis antigen screen, we identified peptides targeted by T cell similarity groups enriched either in controllers or in progressors. We propose that antigens recognized by T cell similarity groups associated with control of infection can be considered as high-priority targets for future vaccine development.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Humans , Tuberculosis/genetics , T-Lymphocytes , Receptors, Antigen, T-Cell/genetics , Antigens , Disease Progression
4.
J Pharm Technol ; 37(5): 254-259, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34752576

ABSTRACT

Background: Inhalation is the preferred method of delivering medication for respiratory conditions such as asthma, chronic obstructive pulmonary disease, and other respiratory disease. A nebulizer converts a medication in liquid form to mist, so that the medication can be inhaled into the lungs. The aim of the study is to systematically review the knowledge, attitude, and practice of patients using nebulization therapy at home. The objective of the study is to review the procedure of nebulizer technique and to interpret the outcome of the studies. Method: Scopus, PubMed, BMJ, and other database from 2000 to 2020 were searched using Boolean operators. Title and abstract were screened for nebulizer technology and for inclusion and exclusion criteria. After full text screening 16 articles were included in the study. Result: Use of nebulizer at home was a challenge at all stages including setting up and operating nebulizer, filling up of medication, inhalation technique, end point dismantling, and maintenance. The main challenge experienced by the participants was with cleaning and disinfecting of nebulizer. There were studies that reported with 71.6% pathogen contamination due to inappropriate cleaning and disinfecting. Conclusion: Patients with respiratory disease using nebulizers at home find difficulty in appropriate and rational use of the device. Apart from the nebulizer user guidelines from the manufactures, it is suggested that a short audio visual demonstrating the appropriate and effective use of nebulizers and also its maintenance in their colloquial language with handout infographics would highly facilitate the effective use of nebulizers.

5.
Foods ; 10(11)2021 Oct 22.
Article in English | MEDLINE | ID: mdl-34828830

ABSTRACT

Value-added phytochemicals from food by-products and waste materials have gained much interest and among them, dietary polyphenolic compounds with potential biological properties extend a promising sustainable approach. Oxyresveratrol (Oxy), a stilbenoid polyphenol, possesses great therapeutic potential, though its pharmacokinetic issues need attention. A good source of oxyresveratrol was found in underutilized coconut shells and the synbiotic applications of the compound in combination with a potential probiotic isolate Limosilactobacillus fermentum ASBT-2 was investigated. The compound showed lower inhibitory effects on the strain with minimum inhibitory concentration (MIC) of 1000 µg/mL. Oxyresveratrol at sub-MIC concentrations (500 µg/mL and 250 µg/mL) enhanced the probiotic properties without exerting any inhibitory effects on the strain. The combination at sub- MIC concentration of the compound inhibited Salmonella enterica and in silico approaches were employed to elucidate the possible mode of action of oxy on the pathogen. Thus, the combination could target pathogens in the gut without exerting negative impacts on growth of beneficial strains. This approach could be a novel perspective to address the poor pharmacokinetic properties of the compound.

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