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Frontiers in immunology
2024;15 1427559.

Understanding the development of tuberculous granulomas: insights into host protection and pathogenesis, a review in humans and animals.

Jiwon Lyu, Drew E Narum, Susan L Baldwin, Sasha E Larsen, Xiyuan Bai, David E Griffith, V��ronique Dartois, Threnesan Naidoo, Adrie J C Steyn, Rhea N Coler, Edward D Chan
Author Information
  1. Jiwon Lyu: Division of Pulmonary and Critical Medicine, Soon Chun Hyang University Cheonan Hospital, Seoul, Republic of Korea.
  2. Drew E Narum: Department of Academic Affairs, National Jewish Health, Denver, CO, United States.
  3. Susan L Baldwin: Center for Global Infectious Diseases, Seattle Children's Research Institute, Seattle, WA, United States.
  4. Sasha E Larsen: Center for Global Infectious Diseases, Seattle Children's Research Institute, Seattle, WA, United States.
  5. Xiyuan Bai: Department of Academic Affairs, National Jewish Health, Denver, CO, United States.
  6. David E Griffith: Department of Medicine, National Jewish Health, Denver, CO, United States.
  7. V��ronique Dartois: Center for Discovery and Innovation, Hackensack Meridian School of Medicine, Nutley, NJ, United States.
  8. Threnesan Naidoo: Departments of Forensic & Legal Medicine and Laboratory Medicine & Pathology, Faculty of Medicine & Health Sciences, Walter Sisulu University, Mthatha, South Africa.
  9. Adrie J C Steyn: Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa.
  10. Rhea N Coler: Center for Global Infectious Diseases, Seattle Children's Research Institute, Seattle, WA, United States.
  11. Edward D Chan: Department of Academic Affairs, National Jewish Health, Denver, CO, United States.
PMID: 39717773 DOI: 10.3389/fimmu.2024.1427559

Abstract

Granulomas, organized aggregates of immune cells which form in response to (), are characteristic but not exclusive of tuberculosis (TB). Despite existing investigations on TB granulomas, the determinants that differentiate host-protective granulomas from granulomas that contribute to TB pathogenesis are often disputed. Thus, the goal of this narrative review is to help clarify the existing literature on such determinants. We adopt the view that TB granulomas are host-protective organelles and discuss the molecular and cellular determinants that induce protective granulomas and those that promote their failure. While reports about protective TB granulomas and their failure may initially seem contradictory, it is increasingly recognized that either deficiencies or excesses of the molecular and cellular components in TB granuloma formation may be detrimental to the host. More specifically, insufficient or excessive expression/representation of the following components have been reported to skew granulomas toward the less protective phenotype: epithelioid macrophages; type 1 adaptive immune response; type 2 adaptive immune response; tumor necrosis factor; interleukin-12; interleukin-17; matrix metalloproteinases; hypoxia in the TB granulomas; hypoxia inducible factor-1 alpha; aerobic glycolysis; indoleamine 2,3-dioxygenase activity; heme oxygenase-1 activity; immune checkpoint; leukotriene A4 hydrolase activity; nuclear-factor-kappa B; and transforming growth factor-beta. Rather, more precise and timely coordinated immune responses appear essential for eradication or containment of infection. Since there are several animal models of infection with , other species within the complex, and the surrogate - whether natural (cattle, elephants) or experimental (zebrafish, mouse, guinea pig, rabbit, mini pig, goat, non-human primate) infections - we also compared the TB granulomatous response and other pathologic lung lesions in various animals infected with one of these mycobacteria with that of human pulmonary TB. Identifying components that dictate the formation of host-protective granulomas and the circumstances that result in their failure can enhance our understanding of the macrocosm of human TB and facilitate the development of novel remedies - whether they be direct therapeutics or indirect interventions - to efficiently eliminate infection and prevent its pathologic sequelae.

Keywords

animal models granuloma immunology lung mycobacteria pathology tuberculosis

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MeSH Term

Animals
Humans
Adaptive Immunity
Cytokines
Granuloma
Host-Pathogen Interactions
Mycobacterium tuberculosis
Tuberculosis

Chemicals

Cytokines
Journal Article Review
Article has an altmetric score of 1

Word Cloud

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