Related Experiment Video
Updated: May 7, 2026
Adipose-Derived Mesenchymal Stromal Cells Co-Cultured with Primary Mixed Glia to Reduce Prion-Induced Inflammation
Published on: August 11, 2023
Alpha-B-crystallin induces an immune-regulatory and antiviral microglial response in preactive multiple sclerosis
Malika Bsibsi1, Inge R Holtman, Wouter H Gerritsen
1From Delta Crystallon BV, Leiden (MB, JMvN); Department of Medical Physiology, University Medical Centre Groningen, Groningen (IRH, BJLE, EB); and Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (WHG, PvdV, SA); and Department of Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom (SA).
Abstract:
Microglial nodules are frequently observed in the normal-appearing white matter of multiple sclerosis (MS) patients. Previously, we have shown that these clusters, which we call "preactive MS lesions," are closely associated with stressed oligodendrocytes and myelin sheaths that contain markedly elevated levels of the small stress protein alpha-B-crystallin (HspB5). Here, we show that microglia in these lesions express the recently identified receptors for HspB5, that is, CD14, Toll-like receptor family 1 and 2 (TLR1 and TLR2), and several molecular markers of the microglial response to HspB5. These markers were identified by genome-wide transcript profiling of 12 primary human microglial cultures at 2 time points after exposure to HspB5. These data indicate that HspB5 activates production by microglia of an array of chemokines, immune-regulatory mediators, and a striking number of antiviral genes that are generally inducible by type I interferons. Together, our data suggest that preactive MS lesions are at least in part driven by HspB5 derived from stressed oligodendrocytes and may reflect a local attempt to restore tissue homeostasis.
Insights
Microglial nodules in multiple sclerosis (MS) lesions are linked to alpha-B-crystallin (HspB5) from stressed cells. HspB5 activates microglia, suggesting a role in tissue repair attempts within the brain.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Molecular Medicine
Background:
- Microglial nodules are common in normal-appearing white matter of multiple sclerosis (MS) patients.
- These "preactive MS lesions" correlate with stressed oligodendrocytes and elevated alpha-B-crystallin (HspB5).
Purpose of the Study:
- To investigate the interaction between HspB5 and microglia in preactive MS lesions.
- To identify molecular markers of microglial activation by HspB5.
Main Methods:
- Genome-wide transcript profiling of human microglial cultures exposed to HspB5.
- Analysis of microglial receptors (CD14, TLR1, TLR2) for HspB5.
Main Results:
- Microglia in preactive MS lesions express HspB5 receptors (CD14, TLR1, TLR2).
- HspB5 triggers microglial production of chemokines, immune mediators, and antiviral genes.
- These antiviral genes are often induced by type I interferons.
Conclusions:
- HspB5 from stressed oligodendrocytes likely drives preactive MS lesions.
- Microglial activation by HspB5 may represent an endogenous attempt to restore tissue homeostasis in MS.
Related Concept Videos
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...