Heat inactivated mycobacteria, alpha-Gal and zebrafish: Insights gained from experiences with two promising trained immunity inductors and a validated animal model

Immunology. 2022 Oct;167(2):139-153. doi: 10.1111/imm.13529. Epub 2022 Jul 12.

Abstract

Trained immunity (TRAIM) may be defined as a form of memory where innate immune cells such as monocytes, macrophages, dendritic and natural killer (NK) cells undergo an epigenetic reprogramming that enhances their primary defensive capabilities. Cross-pathogen protective TRAIM can be triggered in different hosts by exposure to live microbes or microbe-derived products such as heat-inactivated Mycobacterium bovis or with the glycan α-Gal to elicit protective responses against several pathogens. We review the TRAIM paradigm using two models representing distinct scales of immune sensitization: the whole bacterial cell and one of its building blocks, the polysaccharides or glycans. Observations point out to macrophage lytic capabilities and cytokine regulation as two key components in non-specific innate immune responses against infections. The study of the TRAIM response deserves attention to better characterize the evolution of host-pathogen cooperation both for identifying the aetiology of some diseases and for finding new therapeutic strategies. In this field, the zebrafish provides a convenient and complete biological system that could help to deepen in the knowledge of TRAIM-mediated mechanisms in pathogen-host interactions.

Keywords: cross-protection; glycan alpha-Gal; heat-inactivated Mycobacterium bovis; macrophages; trained innate immunity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines
  • Disease Models, Animal
  • Hot Temperature
  • Immunity, Innate
  • Mycobacterium Infections*
  • Mycobacterium bovis*
  • Polysaccharides
  • Zebrafish

Substances

  • Cytokines
  • Polysaccharides