Table 1 Triggers, mechanisms and functions of trained immunity or inflammatory memory in type 2 immune responses.
Trigger | Mechanism | Functional effects | References |
|---|---|---|---|
Helminth infection | |||
N. brasiliensis infection | IL-13 production by neutrophils; IL4Rα-dependent alternative macrophage activation | Enhanced macrophage-mediated killing of Nb larvae, enhanced expression of integrins, Arginase-1 and CCL17 | |
S. venezuelensis infection | IL-33-dependent ILC2 expansion & activation; eosinophil activation | Reduced worm burdens in subsequent Nb infection | |
IL-4 and IL-13 production by eosinophils | Prevention of neuronal loss during subsequent enteric infections | ||
House dust mite extract | Eosinophil expansion and activation (CD4+ T cell dependent) | Improved host defense against Ascaris infection | |
F. hepatica products | Reprogramming of myeloid progenitors in the bone marrow | Long-lasting protection against EAE | |
Type 2 inflammation (allergy, asthma, CRSwNP) | |||
? in non-allergic asthmatics | Reduced DNA methylation, transcriptional reprogramming and aberrant lipid/acylcarnitine metabolism in human MDM | Chronic type 2 airway inflammation by increased CXCL8, CCL20, LTB4 and FAO? | |
House dust mite extract | TNF-dependent reprogramming of human MDM and murine bone marrow progenitors | Enhanced cysLT and CCL17 secretion in type 2 airway inflammation | |
IL-33 | Trained ILC2 display genetic profile similar to memory CD4+ T cells, STAT3-driven epigenetic remodeling? | Increased IL-5, IL-13 secretion, promote Th2 differentiation | |
IL-13 | Epithelial stem cells epigenetically reprogrammed by IL-13? | Disruption of epithelial barrier, chronic type 2 airway inflammation; nasal polyposis? | |
AIT | Tolerance induction of ILC2, monocytes, DCs | Switch to ILC1, increase in anti-inflammatory monocytes and pDCs | |
