Pyogenic Bacterial Infections in Humans with MyD88 Deficiency

TLDR

MyD88 is a critical adaptor for most Toll‑like and interleukin‑1 receptors, and its absence in mice causes heightened susceptibility to diverse pathogens. The study reports on naturally occurring MyD88 deficiency in humans. Nine children with autosomal recessive MyD88 deficiency experienced life‑threatening, recurrent pyogenic bacterial infections, particularly invasive pneumococcal disease, yet remained otherwise healthy, showed age‑related improvement unrelated to cellular leakiness, indicating that MyD88‑dependent TLRs and IL‑1Rs are essential for defense against a limited set of pyogenic bacteria but largely redundant for most natural infections.

Abstract

MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.