Toll-like Receptor 4 Is a Sensor for Autophagy Associated with Innate Immunity

Yi Xu, Chinnaswamy Jagannath, Xian De Liu, Amir Sharafkhaneh, Katarzyna E. Kolodziejska, N. Tony Eissa

Research output: Contribution to journalArticle

645 Scopus citations

Abstract

Autophagy has recently been shown to be an important component of the innate immune response. The signaling pathways leading to activation of autophagy in innate immunity are not known. Here we showed that Toll-like receptor 4 (TLR4) served as a previously unrecognized environmental sensor for autophagy. Autophagy was induced by lipopolysaccharide (LPS) in primary human macrophages and in the murine macrophage RAW264.7 cell line. We defined a new molecular pathway in which LPS-induced autophagy was regulated through a Toll-interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)-dependent, myeloid differentiation factor 88 (MyD88)-independent TLR4 signaling pathway. Receptor-interacting protein (RIP1) and p38 mitogen-activated protein kinase were downstream components of this pathway. This signaling pathway did not affect cell viability, indicating that it is distinct from the autophagic death signaling pathway. We further showed that LPS-induced autophagy could enhance mycobacterial colocalization with the autophagosomes. This study links two ancient processes, autophagy and innate immunity, together through a shared signaling pathway.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalImmunity
Volume27
Issue number1
DOIs
StatePublished - Jul 27 2007

Keywords

  • CELLIMMUNO
  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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