Infectious Agents as Stimuli of Trained Innate Immunity

Paulina Rusek, Mateusz Wala, Magdalena Druszczyńska, Marek Fol, Paulina Rusek, Mateusz Wala, Magdalena Druszczyńska, Marek Fol

Abstract

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.

Keywords: bacille Calmette-Guérin (BCG); chitin; epigenetic reprogramming; innate immune memory; innate immunity training; lipopolysaccharide (LPS); β-glucan.

Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Primary and secondary immune responses in adaptive (panel A) and innate (panel B) immunity. (A) After recognition of an infectious agent, naïve T and B cells transform into antigen-specific effector cells, which can survive as memory cells and respond more robustly to the same infectious agent during secondary infection; (B) Innate immune cells, activated during primary infection, undergo epigenetic reprogramming and become primed to respond more effectively to secondary stimulation caused by a related or unrelated infectious agent.
Figure 2
Figure 2
Potential cell signal-transduction pathways involved in the induction of trained innate immunity. Signaling pathways triggered in the response to certain stimuli lead to cell functional reprogramming associated with epigenetic changes resulting in the regulation of the ensuing cell phenotype. MDP—muramyl dipeptide; NOD2—nucleotide binding oligomerization domain containing 2; Raf-1—Raf-1 proto-oncogene, serine/threonine kinase; RIP2—receptor-interacting protein kinase; FIBCD1—fibrinogen C domain containing 1 protein (although mainly expressed on enterocytes and airway epithelial cells, due to the high homology to the ficolins, it may play an important role in innate immunity).

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