About this Research Topic
Tuberculosis (TB) prevails as a leading killer among infectious diseases of humans worldwide. Mycobacterium Tuberculosis (Mtb), the causative agent of TB, has co-existed with the human host for thousands of years. Tools currently available, including diagnostic modalities to identify patients, vaccines to prevent progression of Mtb infection into active disease, as well as anti-TB drugs are inadequate in fully alleviating the morbidity and mortality associated with TB. Therefore, improved intervention strategies are urgently needed for efficient containment.
Following exposure to Mtb-containing aerosol droplets, the bacteria reach alveoli and interact with the host innate cells, such as macrophages and epithelial cells. Engulfment of Mtb by alveolar macrophages elicits an early immune response that facilitates extravasation of immune cells from the blood to the site of infection, which ultimately leads to formation of the granulomas, a highly organized cellular structure. Although granulomas are thought to contain Mtb infection, the bacteria can resist killing by the host immune cells and persist intracellularly, by employing several virulence mechanisms. This includes resistance to host cell antimicrobial responses, escaping from the phagosome into the cytosol as well as metabolic adaptations to a dormant state. However, the local immunological niche that determines the fate of individual granulomas either towards bacterial containment or failure, is not fully understood. The intricate interactions of the host and pathogen derived factors ultimately determine the outcome of Mtb infection at the cellular and whole organismal level. However, due to the heterogeneity in the virulence of Mtb strains and clinical isolates, as well as the susceptibility/resistance of various host cells, our knowledge on the specific role of these cellular and molecular determinants of Mtb and host cells remains incomplete. Recent evidence also indicates the interplay amongst multiple cellular processes, such as metabolism and epigenetic remodeling in shaping the host immunity to Mtb. Although several in vitro cell culture systems as well as preclinical animal models have been utilised to unravel and understand the various host and bacterial determinants underpinning TB, the inter-connection between various host cellular processes and their impact on Mtb pathogenesis are not fully understood.
Despite recent advances, the intricate host-pathogen interactions and factors that contribute to differential clinical outcomes following Mtb infection remains largely unknown. Therefore, additional studies are needed from both the host and pathogen perspective to delineate the mechanisms underpinning TB pathology. The aim of this research topic is to stimulate discussion among investigators on various host and Mtb characteristics, that would contribute to better understanding of TB and help devise improved diagnosis and treatment options. The scope of this Research Topic is focused on the role of various components of host response, including innate, adaptive and trained immunity and immunometabolism, as well as Mtb virulence determinants and their adaptation features that contribute to TB pathogenesis. We invite original articles, mini reviews, reviews, perspectives and opinion articles that fits within the scope. Articles that address the following themes are particularly encouraged:
· Innate, adaptive and trained immune response in various model systems and humans with TB
· Immunometabolism and its impact on TB.
· Cellular signaling and networks of host cell-Mtb interactions.
· Genes and proteins of Mtb that contribute to TB pathogenesis.
· Target bacterial molecules for potential TB vaccine, drug and diagnostic purposes.
· Preclinical and clinical evaluation of potential vaccines and drugs for TB, including host directed therapy.
· Various pathophysiological states of TB in model systems and in humans.
· Co-morbidity of TB with other infectious and non-infectious diseases.
All of the editors for this Research Topic confirm that they have no conflicts of interest in relation to the publication of this collection.
Following exposure to Mtb-containing aerosol droplets, the bacteria reach alveoli and interact with the host innate cells, such as macrophages and epithelial cells. Engulfment of Mtb by alveolar macrophages elicits an early immune response that facilitates extravasation of immune cells from the blood to the site of infection, which ultimately leads to formation of the granulomas, a highly organized cellular structure. Although granulomas are thought to contain Mtb infection, the bacteria can resist killing by the host immune cells and persist intracellularly, by employing several virulence mechanisms. This includes resistance to host cell antimicrobial responses, escaping from the phagosome into the cytosol as well as metabolic adaptations to a dormant state. However, the local immunological niche that determines the fate of individual granulomas either towards bacterial containment or failure, is not fully understood. The intricate interactions of the host and pathogen derived factors ultimately determine the outcome of Mtb infection at the cellular and whole organismal level. However, due to the heterogeneity in the virulence of Mtb strains and clinical isolates, as well as the susceptibility/resistance of various host cells, our knowledge on the specific role of these cellular and molecular determinants of Mtb and host cells remains incomplete. Recent evidence also indicates the interplay amongst multiple cellular processes, such as metabolism and epigenetic remodeling in shaping the host immunity to Mtb. Although several in vitro cell culture systems as well as preclinical animal models have been utilised to unravel and understand the various host and bacterial determinants underpinning TB, the inter-connection between various host cellular processes and their impact on Mtb pathogenesis are not fully understood.
Despite recent advances, the intricate host-pathogen interactions and factors that contribute to differential clinical outcomes following Mtb infection remains largely unknown. Therefore, additional studies are needed from both the host and pathogen perspective to delineate the mechanisms underpinning TB pathology. The aim of this research topic is to stimulate discussion among investigators on various host and Mtb characteristics, that would contribute to better understanding of TB and help devise improved diagnosis and treatment options. The scope of this Research Topic is focused on the role of various components of host response, including innate, adaptive and trained immunity and immunometabolism, as well as Mtb virulence determinants and their adaptation features that contribute to TB pathogenesis. We invite original articles, mini reviews, reviews, perspectives and opinion articles that fits within the scope. Articles that address the following themes are particularly encouraged:
· Innate, adaptive and trained immune response in various model systems and humans with TB
· Immunometabolism and its impact on TB.
· Cellular signaling and networks of host cell-Mtb interactions.
· Genes and proteins of Mtb that contribute to TB pathogenesis.
· Target bacterial molecules for potential TB vaccine, drug and diagnostic purposes.
· Preclinical and clinical evaluation of potential vaccines and drugs for TB, including host directed therapy.
· Various pathophysiological states of TB in model systems and in humans.
· Co-morbidity of TB with other infectious and non-infectious diseases.
All of the editors for this Research Topic confirm that they have no conflicts of interest in relation to the publication of this collection.
Keywords: Tuberculosis, Mycobacterium, latency, reactivation, subclinical TB, TB, immune response, genetics, virulence, preclinical models, vaccines and drugs
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