Different Regulation of Interleukin-1 Production and Activity in Monocytes and Macrophages: Innate Memory as an Endogenous Mechanism of IL-1 Inhibition

Abstract

Production and activity of interleukin (IL)-1β are kept under strict control in our body, because of its powerful inflammation-promoting capacity. Control of IL-1β production and activity allows IL-1 to exert its defensive activities without causing extensive tissue damage. Monocytes are the major producers of IL-1β during inflammation, but they are also able to produce significant amounts of IL-1 inhibitors such as IL-1Ra and the soluble form of the decoy receptor IL-1R2, in an auto-regulatory feedback loop. Here, we investigated how innate immune memory could modulate production and activity of IL-1β by human primary monocytes and monocyte-derived tissue-like/deactivated macrophages in vitro. Cells were exposed to Gram-negative (Escherichia coli) and Gram-positive (Lactobacillus acidophilus) bacteria for 24 h, then allowed to rest, and then re-challenged with the same stimuli. The presence of biologically active IL-1β in cell supernatants was calculated as the ratio between free IL-1β (i.e., the cytokine that is not bound/inhibited by sIL-1R2) and its receptor antagonist IL-1Ra. As expected, we observed that the responsiveness of tissue-like/deactivated macrophages to bacterial stimuli was lower than that of monocytes. After resting and re-stimulation, a memory effect was evident for the production of inflammatory cytokines, whereas production of alarm signals (chemokines) was minimally affected. We observed a high variability in the innate memory response among individual donors. This is expected since innate memory largely depends on the previous history of exposure or infections, which is different in different subjects. Overall, innate memory appeared to limit the amount of active IL-1β produced by macrophages in response to a bacterial challenge, while enhancing the responsiveness of monocytes. The functional re-programming of mononuclear phagocytes through modulation of innate memory may provide innovative approaches in the management of inflammatory diseases, as well as in the design of new immunization strategies. In this respect, the interindividual variability in innate memory suggests the need of a personalized assessment.

Surface modification of silver nanoparticle (AgNP) by liposomal encapsulation mitigates AgNP-induced inflammation

“…Macrophages unlike monocytes do not readily secrete IL-1β based on our findings and those from other studies (Carta et al, 2011;Madej et al, 2017), this may be attributed to the tissue resident role of macrophages which is less involved promoting inflammation rather than secretion of chemokine required for recruitment of immune cells (Madej et al, 2017). This line of evidence supports our finding that TDMs used in this study secrete significantly higher IL-8 than monocytic THP1.…”

Trained Immunity for Personalized Cancer Immunotherapy: Current Knowledge and Future Opportunities

“…Priming of human monocytes and monocyte-derived macrophages with LPS, an integral component of bacterial endotoxin (TLR4 ligand), or zymosan, a polysaccharide which belongs to the fungal cell wall (TLR2 and Dectin-1 ligand), has been shown to be cross-reactive (LPS-or -zymosan-primed monocytes can react to either stimulus), albeit with a dependence of the dose of the stimulus (Madej et al, 2017). Importantly, IL-1β production by macrophages initially primed by LPS or Escherichia coli is markedly reduced following re-exposure, although in monocytes re-exposure to E. coli, but not LPS, produced much higher amounts of IL-1β (Madej et al, 2017). This observation strongly hinted at the exposure of monocytic cells to one type of pathogen affording immune reactivity to another, i.e., bacteria vs. fungi.…”

Innate Immune Memory in Invertebrate Metazoans: A Critical Appraisal

“…This may however translate, in the long term, also into decreased resistance to infections or increased side effects ( 49 , 50 ). The analytical tools for evaluating innate immune memory are increased resistance to infections in vivo in the whole animal/individual, or a simple evaluation of cytokine production, gene expression, or up/down-regulation of surface markers in monocytes or macrophages challenged in culture after a priming in vivo or in vitro ( 7 , 51 ). It is important to note that the phenomena of potentiation and tolerance are those that we can observe at the level of the entire organism, while at the level of single cells/cell populations we can observe a re-programming of their activation in directions that cannot be immediately ascribed to overall potentiation or overall tolerance ( 52 ).…”