Abstract | PURPOSE: METHODS: We sequenced TLR3 and assessed the impact of the mutations identified. We tested dermal fibroblasts from a patient with EV71 encephalitis and a TLR3 mutation and other patients with known genetic defects of TLR3 or related genes, assessing the response of these cells to TLR3 agonist poly(I:C) stimulation and EV71 infection. RESULTS: Three children with EV71 encephalitis were heterozygous for rare mutations-TLR3 W769X, E211K, and R867Q-all of which were shown to affect TLR3 function. Furthermore, fibroblasts from the patient heterozygous for the W769X mutation displayed an impaired, but not abolished, response to poly(I:C). We found that TLR3-deficient and TLR3-heterozygous W769X fibroblasts were highly susceptible to EV71 infection. CONCLUSIONS: Autosomal dominant TLR3 deficiency may underlie severe EV71 infection with encephalitis. Human TLR3 immunity is essential to protect the central nervous system against HSV-1 and EV71. Children with severe EV71 infections, such as encephalitis in particular, should be tested for inborn errors of TLR3 immunity.
|
Authors | Chen-Yen Kuo, Cheng-Lung Ku, Hye-Kyung Lim, Shao-Hsuan Hsia, Jainn-Jim Lin, Chia-Chi Lo, Jing-Ya Ding, Rei-Lin Kuo, Jean-Laurent Casanova, Shen-Ying Zhang, Luan-Yin Chang, Tzou-Yien Lin |
Journal | Journal of clinical immunology
(J Clin Immunol)
Vol. 42
Issue 3
Pg. 606-617
(04 2022)
ISSN: 1573-2592 [Electronic] Netherlands |
PMID | 35040013
(Publication Type: Journal Article)
|
Copyright | © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. |
Chemical References |
- TLR3 protein, human
- Toll-Like Receptor 3
- Poly I-C
|
Topics |
- Cells, Cultured
- Child
- Encephalitis, Herpes Simplex
(diagnosis, genetics)
- Encephalitis, Viral
(diagnosis, genetics)
- Enterovirus
- Enterovirus A, Human
(genetics)
- Enterovirus Infections
(diagnosis, genetics)
- Humans
- Poly I-C
- Toll-Like Receptor 3
(genetics)
|