Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Pediatrics, Allergy and Clinical Immunology Unit, Royal Hospital, Muscat, Oman.
Clin Immunol. 2019 Oct;207:40-42. doi: 10.1016/j.clim.2019.07.004. Epub 2019 Jul 10.
Mutations in MYD88 cause susceptibility to invasive bacterial infections through impaired signaling downstream of toll-like receptors (TLRs) and IL-1 receptors. We studied a patient presenting with neutropenia, delayed umbilical cord separation, BCG adenitis, andP. aeruginosapneumonia. Next-generation DNA sequencing identified a novel homozygous truncation mutation in MYD88 that abolishes MyD88 expression. The patient's dermal fibroblasts had severely impaired IL-6 production after stimulation with ligands for the MyD88-dependent receptors TLR2, TLR4 and IL-1R, while responses to ligands for the MyD88-independent receptors TLR3 and TNF-α were preserved. Notably, secretion of TNF-α, which is essential for BCG control, was also impaired after LPS stimulation. In this first report of BCG infection in MyD88 deficiency, data suggest that MyD88-dependent TNF-α production contributes to control of mycobacterial disease.
MYD88 突变通过影响 Toll 样受体 (TLR) 和 IL-1 受体下游信号转导，导致易发生侵袭性细菌感染。我们研究了一位中性粒细胞减少症、脐带延迟分离、卡介苗（BCG）淋巴结炎和绿脓杆菌肺炎患者。下一代 DNA 测序在 MYD88 中发现了一种新的纯合截短突变，该突变导致 MyD88 表达缺失。患者的真皮成纤维细胞在受到 MyD88 依赖性受体 TLR2、TLR4 和 IL-1R 的配体刺激后，IL-6 的产生严重受损，而对 MyD88 非依赖性受体 TLR3 和 TNF-α 的配体的反应则保持不变。值得注意的是，BCG 控制所必需的 TNF-α的分泌在 LPS 刺激后也受到了损害。在这首例 MYD88 缺陷导致的 BCG 感染报告中，数据表明，MyD88 依赖性 TNF-α 的产生有助于控制分枝杆菌病。
