Table 2.
Metabolic effects on immune cells impact immune regulation.
| Parasite infection or stimuli | Treatment or model | Metabolic effects in immune cells | Metabolic effects at tissue and systemic level | References |
|---|---|---|---|---|
| Secretion of IL-4 | — | Promotion of OXPHOS and mitochondrial respiration in M2 macrophages surrounding the parasite | — | (5) |
| Activation of M2 macrophages with IL-4 | Bone marrow-derived macrophages isolated from femurs and tibias, stimulated with murine IL-4 | Enhanced FAO promoted by STAT6 and PGC1β. Inhibition of proinflammatory cytokine production | — | (5, 106) |
| IL-4R signaling in M2 macrophages | Myeloid-cell-specific IL-4Rα-deficient mice (Il4ra fl/− Lyz2-cre) and Retnla −/− mice | M2 macrophages activated by IL-4R signaling express IGF-1, RELMα and Arg-1. RELMα and Arg-1 enhance wound healing. | — | (104, 107) |
| Stimulation with IL-4 | CD36 expression induced by IL-4 in RAW 264.7 cells | Induction of CD36 expression and lysosomal function with endocytosis of LDL and VLDL | — | (108) |
| Brugia malayi | Human monocyte-derived dendritic cells exposed to B. malayi microfilaria from infected jirds | Downregulation of components of the mTOR signaling pathway in microfilaria-induced DC. Inhibition of mTOR and its regulatory proteins phosphorylation which are vital for protein synthesis in DC. Increased autophagy | — | (109) |
| Nippostrongylus brasiliensis | RIP2-Opa1KO mice with pancreatic β cell Opa1 deficiency, infected trough subcutaneous inoculation of third stage N. brasiliencis larvae | — | Increase in WAT eosinophils and M2 macrophages with increased expression of M2 markers (YM1 and Arg-1). Increase in body insulin sensitivity and glucose tolerance, diminished hepatic steatosis | (41, 110) |
| Heligmosomoides polygyrus | C57BL/6 mice fed with high-fat diet and infected with 200 third stage H. polygyrus larvae | — | Decreased weight gain, increase in glucose tolerance and WAT beiging. Increase in WAT M2 gene expression and M2 markers | (41, 111) |
| Fasciola hepatica | Bone marrow-derived macrophages and peritoneal macrophages from C57BL/6 mice, stimulated with synthetic FhHDM-1 | FhDHM-1 reprograms macrophages by inducing OXPHOS and elevation of glutaminolysis, resulting in inhibition of pro-inflammatory cytokines (TNF and IL-6) independent of M2 polarization. Inhibition of lysosomal vATPSase. | — | (112) |
| Schistosoma mansoni | Arg1(-/flox); LysMcre mice and Arg1(flox/flox);Tie2cre mice | Macrophage expression of Arg-1, triggered by S. mansoni infection, downregulates inflammation and T proliferation by depleting arginine concentrations. Arg-1 expressing macrophages have an anti-fibrotic activity during Th2 response, and are important mediators of immune modulation of chronic schistosomiasis | — | (113) |
| Heligmosomoides polygyrus | A 2B AR −/− BL/6 mice infected with third stage H. polygyrus larvae trough oral administration | Adenosine initiates a helminth-induced type 2 response through interaction with the A2B adenosine receptor. Upregulation of IL-33 and the subsequent activation of ILC2 cells | — | (104, 114) |
Acronyms, OXPHOS, oxidative phosphorylation; Arg-1, arginase 1; WAT, white adipose tissue; RELMα, resistin-like molecule alpha. FhHDM-1, Fasciola hepatica helminth defense molecule; DC, dendritic cell. mTOR, mammalian target of rapamycin.
—, Not determined.