Journal
JOURNAL OF IMMUNOLOGY
Volume 195, Issue 10, Pages 4913-4921Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1500953
Keywords
-
Categories
Funding
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases
Ask authors/readers for more resources
Neuronal apoptosis is a key aspect of many different neurologic diseases, but the mechanisms remain unresolved. Recent studies have suggested a mechanism of innate immune-induced neuronal apoptosis through the stimulation of endosomal TLRs in neurons. TLRs are stimulated both by pathogen-associated molecular patterns as well as by damage-associated molecular patterns, including microRNAs released by damaged neurons. In the present study, we identified the mechanism responsible for TLR7/TLR9-mediated neuronal apoptosis. TLR-induced apoptosis required endosomal localization of TLRs but was independent of MyD88 signaling. Instead, apoptosis required the TLR adaptor molecule SARM1, which localized to the mitochondria following TLR activation and was associated with mitochondrial accumulation in neurites. Deficiency in SARM1 inhibited both mitochondrial accumulation in neurites and TLR-induced apoptosis. These studies identify a non-MyD88 pathway of TLR7/TLR9 signaling in neurons and provide a mechanism for how innate immune responses in the CNS directly induce neuronal damage.
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