2. Academic Validation
  3. Heat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally

Heat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally

  • iScience. 2024 Jan 11;27(2):108869. doi: 10.1016/j.isci.2024.108869.
Luna Minute 1 2,  Marta Bergón-Gutiérrez 1 2,  Pablo Mata-Martínez 1 2,  Jaime Fernández-Pascual 1 2,  Verónica Terrón 1 3,  Laura Bravo-Robles 1 2,  Gülce Bıçakcıoğlu 1 2,  Gabriela Zapata-Fernández 1 2,  Nacho Aguiló 4 5,  Eduardo López-Collazo 1 3 5,  Carlos Del Fresno 1 2
Affiliations

Affiliations

  • 1 The Innate Immune Response Group, IdiPAZ, La Paz University Hospital, Madrid, Spain.
  • 2 Immunomodulation Laboratory, IdiPAZ, La Paz University Hospital, Madrid, Spain.
  • 3 Tumor Immunology Laboratory, IdiPAZ, La Paz University Hospital, Madrid, Spain.
  • 4 Department of Microbiology, Pediatrics, Radiology, and Public Health, University of Zaragoza/IIS Aragon, Zaragoza, Spain.
  • 5 CIBERES, CIBERINFEC, Carlos III Health Institute, Madrid, Spain.
PMID: 38318361 DOI: 10.1016/j.isci.2024.108869
Abstract

Trained immunity (TI) represents a memory-like process of innate immune cells. TI can be initiated with various compounds such as Fungal β-glucan or the tuberculosis vaccine, Bacillus Calmette-Guérin. Nevertheless, considering the clinical applications of harnessing TI against infections and Cancer, there is a growing need for new, simple, and easy-to-use TI inducers. Here, we demonstrate that heat-killed Mycobacterium tuberculosis (HKMtb) induces TI both in vitro and in vivo. In human monocytes, this effect represents a truly trained process, as HKMtb confers boosted inflammatory responses against various heterologous challenges, such as lipopolysaccharide (Toll-like Receptor [TLR] 4 ligand) and R848 (TLR7/8 ligand). Mechanistically, HKMtb-induced TI relies on epigenetic mechanisms in a Syk/HIF-1α-dependent manner. In vivo, HKMtb induced TI when administered both systemically and intranasally, with the latter generating a more robust TI response. Summarizing, our research has demonstrated that HKMtb has the potential to act as a mucosal immunotherapy that can successfully induce trained responses.

Keywords

Immune response; Microbiology; Therapy.

Figures
Products