Lim HK, et al. Severe influenza pneumonitis in children with inherited TLR3 deficiency. J Exp Med. 2019 Jun 19.
Autosomal recessive IRF7 and IRF9 deficiencies impair type I and III IFN immunity and underlie severe influenza pneumonitis. We report three unrelated children with influenza A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare TLR3 variants (P554S in two patients and P680L in the third) causing autosomal dominant (AD) TLR3 deficiency. AD TLR3 deficiency can underlie herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic type I IFN immunity to HSV-1. TLR3-mutated leukocytes produce normal levels of IFNs in response to IAV. In contrast, TLR3-mutated fibroblasts produce lower levels of IFN-β and -λ, and display enhanced viral susceptibility, upon IAV infection. Moreover, the patients´ iPSC-derived pulmonary epithelial cells (PECs) are susceptible to IAV. Treatment with IFN-α2b or IFN-λ1 rescues this phenotype. AD TLR3 deficiency may thus underlie IAV-ARDS by impairing TLR3-dependent, type I and/or III IFN-mediated, PEC-intrinsic immunity. Its clinical penetrance is incomplete for both IAV-ARDS and HSE, consistent with their typically sporadic nature.
See Also:
Latest articles in those days:
- The critical role of RAGE in severe influenza infection: A target for control of inflammatory response in the disease 19 minute(s) ago
- Human infection caused by avian influenza A (H10N5) virus 23 minute(s) ago
- Cross-species spill-over potential of the H9N2 bat influenza A virus 13 hours ago
- Bat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets 13 hours ago
- Epidemiological characteristics of human infections with avian influenza A(H5N6) virus, China and Laos: A multiple case descriptive analysis, February 2014-June 2023 1 days ago
[Go Top] [Close Window]