Journal
ISCIENCE
Volume 24, Issue 8, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2021.102845
Keywords
-
Categories
Funding
- National Institutes of Health [R33 AI105944-04, R01 HL133190-01, 1R01GM120272, R01CA218500]
Ask authors/readers for more resources
Macrophages play a crucial role in host immunity and tissue homeostasis, with different activation programs leading to distinct functions. Imbalance of M1 and M2 macrophages can perpetuate chronic inflammation. Rocaglates sensitize macrophages to combat bacterial pathogens more effectively, showing potential for immunomodulation.
Macrophages contribute to host immunity and tissue homeostasis via alternative activation programs. M1-like macrophages control intracellular bacterial pathogens and tumor progression. In contrast, M2-like macrophages shape reparative microenvironments that can be conducive for pathogen survival or tumor growth. An imbalance of these macrophages phenotypes may perpetuate sites of chronic unresolved inflammation, such as infectious granulomas and solid tumors. We have found that plant-derived and synthetic rocaglates sensitize macrophages to low concentrations of the M1-inducing cytokine IFN-gamma and inhibit their responsiveness to IL-4, a prototypical activator of the M2-like phenotype. Treatment of primary macrophages with rocaglates enhanced phagosome-lysosome fusion and control of intracellular mycobacteria. Thus, rocaglates represent a novel class of immunomodulators that can direct macrophage polarization toward the M1-like phenotype in complex microenvironments associated with hypofunction of type 1 and/or hyperactivation of type 2 immunity, e.g., chronic bacterial infections, allergies, and, possibly, certain tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available