CD4+ Th1 and Th17 responses and multifunctional CD8 T lymphocytes associated with cure or disease worsening in human visceral leishmaniasis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 12, 2024

Introduction In VL, a proinflammatory phenotype is typically associated with enhanced phagocytosis and Th1 mediated immune response resulting in infection control. contrast, an anti-inflammatory phenotype, predominant regulatory response, enables intracellular multiplication of Leishmania parasites disease progression. Methods To investigate the impact chemotherapy on Th2 Th17 responses patients visceral leishmaniasis (VL), we assessed all combinations expression IFN-γ, IL-10, IL-4 IL-17 CD4 + CD8 T cell populations peripheral blood mononuclear (PBMC) samples from patients, after antigenic stimulation lysate, throughout treatment follow-up. As increases spleen liver sizes decreases hematocrit, hemogloblin, erythrocytes, monocytes, leukocytes platelets levels are strongly related to disease, studied correlations between frequencies cells producing afore mentioned cytokines, individually combination, these variables, as markers or cure. Results We found that frequency IFN-γ-producingCD4 increased until end Glucantime® AmBisome ®, while IL-17-producing peaked day 7 following start treatment. Although decreased during increase was observed clinical The only IFN-γ correlated monocytes levels. Frequencies double-producers IL-10 positively eosinophils Together, this suggest drives towards at negatively circulating monocyte levels, both single-producers 21 90 7, 30 IL-17, 180. single- cytokines indicative producers three four were low alone disease: 1) single 2) double platelet, leukocyte, lymphocyte 3) triple-producers leukocyte neutrophil 4) IL-4, simultaneously size, Discussion Our results confirmed improvement VL correlates decrease recovery CD4+ IL-17.

Language: Английский

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Intravenous vaccination with BCG against tuberculosis: Strengths and questions deserving further research

Vaccine, Journal Year: 2025, Volume and Issue: unknown, P. 126666 - 126666

Published: Jan. 1, 2025

Language: Английский

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Developing next-generation tuberculosis vaccines based on pathogen–host interactions: Towards a holistic perspective

hLife, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Tuberculosis: An Update for the Clinician

Respirology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

ABSTRACT Tuberculosis (TB) remains a significant global health threat with high mortality and efforts to meet WHO End TB Strategy milestones are off‐track. It has become clear that is not dichotomous infection latent active forms but presents along disease spectrum. Subclinical plays larger role in transmission than previously thought. Aerosol studies have shown undiagnosed patients, even paucibacillary disease, can be highly infectious significantly contribute spread. Encouraging clinical results been seen the M72/AS01 E vaccine. If preliminary confirmed ongoing trials, modelling shows vaccine positively impact epidemic. preventive therapy (TPT), especially for high‐risk groups like people living HIV household contacts of drug‐resistant efficacy implementation resource intensive. Treatment options patients grown rapidly. New shorter, all‐oral treatment regimens represent breakthrough, progress threatened by rising resistance bedaquiline. Many new chemical entities entering trials raise hopes all‐new could overcome rates conventional agents. More research needed on management complex cases, such as central nervous system severe HIV‐associated TB. Post‐TB lung (PTLD) an under‐recognised growing concern, affecting millions survivors lasting respiratory impairment increased mortality. Continued investment development vaccines therapeutics, shortening, sequelae critical combat this public challenge.

Language: Английский

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Sensing mycobacteria through unconventional pathways

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: 135(6)

Published: March 16, 2025

Approximately one-quarter of the global population is estimated to be infected with Mycobacterium tuberculosis. New developments in vaccine design and therapeutics are urgently needed, particularly face multidrug-resistant tuberculosis (TB). In this issue JCI, Sakai colleagues used a multidisciplinary approach determine that trehalose-6-monomycolate (TMM), mycobacterial cell wall lipid, serves as T antigen presented by CD1b. CD1b-TMM–specific cells were characterized conserved receptor features present at elevated frequencies individuals active TB disease. These findings highlight dual role TMM stimulating both innate adaptive immunity broaden our understanding CD1-mediated lipid recognition unconventional cells.

Language: Английский

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