Pyogenic Bacterial Infections in Humans with MyD88 Deficiency

By H. von Bernuth, C. Picard, Zhongbo Jin, Rungnapa Pankla, Hui Xiao, Cheng-Lung Ku, Maya Chrabieh, I. Mustapha, P. Ghandil, Y. Camcıoğlu and 28 more. Science, 2003

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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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/7a8c3f9399784223ede6e265d6826cb93aecd09c

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In Immunology

Citations in the corpus

30 years of NF-κB: a blossoming of relevance to human pathobiology (2017, positive): “…differentiation primary response 88) and IRAK4 (interleukin 1 receptor associated kinase 4) cause clinically indistinguishable phenotypes, characterized by life-threatening, recurrent pyogenic bacterial infections, especially by invasive pneumococci (Picard et al., 2003; von Bernuth et al., 2008).”
Pattern recognition receptors in health and diseases (2021, background): “MyD88 has a TIR domain at the C-terminus and a death domain at the Nterminus and is the linker molecule in most TLR signal transduction pathways.(257) The current research indicated that, in the MyD88dependent pathway, MyD88 signaling mainly leads to the production of pro-inflammatory cytokines, suc”
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses (2009, background): “However, a similar immunological and infectious phenotype was recently described in the case of MyD88-deficient patients, who are vulnerable to recurrent pyogenic infections early in life (376), supporting a narrow but nonredundant role of both IRAK4 and MyD88 in protective immunity against certain ”
Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. (2011, background): “…five PIDs with impaired TLR signaling pathways have been described: autosomal-recessive MyD88, IRAK4, and UNC93B1 deficiency and autosomal-dominant TLR3 and TRAF3 deficiency (Casrouge et al., 2006; Pérez de Diego et al., 2010; Picard et al., 2003; von Bernuth et al., 2008; Zhang et al., 2007).”
Human CD14dim Monocytes Patrol and Sense Nucleic Acids and Viruses via TLR7 and TLR8 Receptors (2010, positive): “…from the peripheral blood of patients deficient in myeloid differentiation primary response gene 88 (MYD88) and in some cases in interleukin-1 receptor-associated kinase 4 (IRAK-4) (Picard et al., 2003; von Bernuth et al., 2008) and from controls and were stimulated with measles virus and/or HSV1.”