The discoveries made over the past few years have modified the current immunological paradigm. It turns out that innate immunity cells can mount some kind of immunological memory, similar to that observed in the acquired immunity and corresponding to the defense mechanisms of lower organisms, which increases their resistance to reinfection. This phenomenon is termed trained innate immunity. It is based on epigenetic changes in innate immune cells (monocytes/macrophages, NK cells) after their stimulation with various infectious or non-infectious agents. Many infectious stimuli, including bacterial or fungal cells and their components (LPS, β-glucan, chitin) as well as viruses or even parasites are considered potent inducers of innate immune memory. Epigenetic cell reprogramming occurring at the heart of the phenomenon may provide a useful basis for designing novel prophylactic and therapeutic strategies to prevent and protect against multiple diseases. In this article, we present the current state of art on trained innate immunity occurring as a result of infectious agent induction. Additionally, we discuss the mechanisms of cell reprogramming and the implications for immune response stimulation/manipulation.

Recent advances in microbiome research have uncovered a dynamic and complex connection between the gut and lungs, known as the gut–lung axis. This bidirectional communication network plays a critical role in modulating immune responses and maintaining respiratory health. Mediated by immune interactions, metabolic byproducts, and microbial communities in both organs, this axis demonstrates how gut-derived signals, such as metabolites and immune modulators, can reach the lung tissue via systemic circulation, influencing respiratory function and disease susceptibility. To explore the implications of this connection, we conducted a systematic review of studies published between 2001 and 2024 (with as much as nearly 60% covering the period 2020–2024), using keywords such as “gut–lung axis”, “microbiome”, “respiratory disease”, and “immune signaling”. Studies were selected based on their relevance to gut–lung communication mechanisms, the impact of dysbiosis, and the role of the gut microbiota in respiratory diseases. This review provides a comprehensive overview of the gut–lung microbiome axis, emphasizing its importance in regulating inflammatory and immune responses linked to respiratory health. Understanding this intricate pathway opens new avenues for microbiota-targeted therapeutic strategies, which could offer promising interventions for respiratory diseases like asthma, chronic obstructive pulmonary disease, and even infections. The insights gained through this research underscore the potential of the gut–lung axis as a novel target for preventative and therapeutic approaches in respiratory medicine, with implications for enhancing both gut and lung health.

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 development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

Some intracellular pathogens are able to avoid the defense mechanisms contributing to host epigenetic modifications. These changes trigger alterations tothe chromatin structure and on the transcriptional level of genes involved in the pathogenesis of many bacterial diseases. In this way, pathogens manipulate the host cell for their own survival. The better understanding of epigenetic consequences in bacterial infection may open the door for designing new vaccine approaches and therapeutic implications. This article characterizes selected intracellular bacterial pathogens, including Mycobacterium spp., Listeria spp., Chlamydia spp., Mycoplasma spp., Rickettsia spp., Legionella spp. and Yersinia spp., which can modulate and reprogram of defense genes in host innate immune cells.