Cytokine receptors are critical regulators of the antimycobacterial immune response, playing a key role in initiating and coordinating the recruitment and activation of immune cells during infection. They recognize and bind specific cytokines and are involved in inducing intracellular signal transduction pathways that regulate a diverse range of biological functions, including proliferation, differentiation, metabolism and cell growth. Due to mutations in cytokine receptor genes, defective signaling may contribute to increased susceptibility to mycobacteria, allowing the pathogens to avoid killing and immune surveillance. This paper provides an overview of cytokine receptors important for the innate and adaptive immune responses against mycobacteria and discusses the implications of receptor gene defects for the course of mycobacterial infection.
The Bacillus Calmette–Guérin (BCG) vaccine, best known for its role in preventing tuberculosis, has recently garnered attention for its broader immunomodulatory effects. By inducing trained immunity, BCG reprograms innate immune cells, enhancing their responses to various pathogens. This process, driven by epigenetic and metabolic reprogramming, suggests that BCG may have therapeutic potential far beyond tuberculosis. Emerging evidence points to its potential benefits in conditions such as autoimmune diseases, cancer, and viral infections. Furthermore, by modulating immune activity, BCG has been proposed to reduce chronic inflammation and promote immune tolerance. This review delves into the multifaceted role of BCG, highlighting its potential as a versatile therapeutic tool for managing a wide range of diseases.
The innate immune system recognizes pathogen-associated molecular motifs through pattern recognition receptors (PRRs) that induce inflammasome assembly in macrophages and trigger signal transduction pathways, thereby leading to the transcription of inflammatory cytokine genes. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) represent a family of cytosolic PRRs involved in the detection of intracellular pathogens such as mycobacteria or viruses. In this review, we discuss the role of NOD1, NOD2, and NLRC5 receptors in regulating antiviral and antimycobacterial immune responses by providing insight into molecular mechanisms as well as their potential health and disease implications.
Over the past decade, a group of lymphocyte-like cells called innate lymphoid cells (ILCs) has gained considerable attention due to their crucial role in regulating immunity and tissue homeostasis. ILCs, lacking antigen-specific receptors, are a group of functionally differentiated effector cells that act as tissue-resident sentinels against infections. Numerous studies have elucidated the characteristics of ILC subgroups, but the mechanisms controlling protective or pathological responses to pathogens still need to be better understood. This review summarizes the functions of ILCs in the immunology of infections caused by different intracellular and extracellular pathogens and discusses their possible therapeutic potential.
Background: Children have an increased risk of developing active tuberculosis (TB) after exposure to Mycobacterium tuberculosis (M.tb), and they are more likely to develop the most severe forms of TB. Rapid diagnosis and treatment of latent M.tb infection (LTBI) is essential to lessen the devastating consequences of TB in children. Objective: The aim of the study was to evaluate TST (tuberculin skin test) and IGRA (interferon-gamma release assay) utility in identifying LTBI in a cohort of Bacille Calmette–Guérin (BCG)-vaccinated Polish children and adolescents exposed or not exposed to contagious TB. In addition, we asked whether quantitative assessment of IGRA results could be valuable in predicting active TB disease. Results: Of the 235 recruited volunteers, 89 (38%) were TST-positive (TST+), 74 (32%) were IGRA-positive (IGRA+), and 62 (26%) were both TST+ and IGRA+. The frequency of TST positivity was significantly higher in the group with (59%) than without TB contact (18%). The percentage of TST+ subjects increased with age from 36% in the youngest children (10 years). All positive IGRA results were found solely in the group of children with TB contact. There was a significant increase in the rate of positive IGRA results with age, from 9% in the youngest to 48% in the oldest group. The 10 mm TST cutoff showed good sensitivity and specificity in both TB exposed and nonexposed children and was associated with excellent negative predictive value, especially among nonexposed volunteers. Mean IFN-γ concentrations in IGRA cultures were significantly higher in the group of LTBI compared to the children with active TB disease, both TST+ and TST−. Conclusions: Both TST and IGRA can be used as screening tests for BCG-vaccinated children and adolescents exposed to contagious TB.
1 January 2025 in Archivum Immunologiae et Therapiae Experimentalis
Studies on the bacillus Calmette–Guérin (BCG) vaccine, traditionally used against tuberculosis, indicate its potential benefit in protecting against infections. The vaccine’s ability to broadly activate the immune system suggests its potential to bolster non-specific immunity, which could be crucial for combating respiratory pathogens. This study aimed to evaluate the messenger RNA (mRNA) expression of interferon (IFN)-α, IFN-β, and IFN-γ as well as the secretion of these cytokines in whole blood co-stimulated cultures with BCG and antigens of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV) from BCG-vaccinated Polish children who have been infected or uninfected with RSV and/or SARS-CoV-2. Significant differences were observed in the secretion and mRNA expression of IFN-α and IFN-γ in response to RSV antigens in all groups of children studied. When cultures were conducted in the presence of SARS-CoV-2 antigens, live BCG did not induce increased IFN-α secretion compared with cultures stimulated with these antigens alone. However, enhanced secretion was observed for IFN-γ, and no such relationship was observed for mRNA expression. Furthermore, discrepancies between IFN-β secretion and mRNA expression were observed, suggesting that IFN protein secretion can also be controlled at the translational or posttranslational level. The data from our studies indicate that BCG vaccination may modulate the IFN response to viral challenges with SARS-CoV-2 and RSV, suggesting a potential immunoregulatory role.