Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. (Immunity, 2007, 27(1):135-144.)

報告日期: 2007/10/02
報告時間: 15:10/16:00
報告學生: 王琪芸 (英文報告)
講評老師: 葉才明
附件下載:

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

Xu et al., 2007. Immunity 27: 135-144.

Student: Chi-Yun Wang (王琪芸)

Commentator: Dr. Trai-Ming Yeh (葉才明博士)

Time: 15:10-16:00, Oct. 2, 2007

Place: Room 602

 

Abstract:

In innate immunity, autophagy confers host defence to eliminate bacterial pathogens, including group A Streptococcus, Shegella flexineri and Mycobacterium tuberculosis (1). Current studies showed that class III phosphatidylinositol 3-kinases (PI3Ks) are essential for starvation-induced autophagy. However, it is still unknown what signaling pathway contributes to the induction of pathogen-induced autophagy. In this paper (2), the authors investigated the role of Toll-like receptor 4 (TLR4) in autophagy. Results showed that lipopolysaccharide (LPS)/TLR4 signaling induced autophagy in primary human macrophages and murine RAW264.7 macrophages. Furthermore, the induction of LPS-induced autophagy was Toll-interleukin-1 receptor domain-containing adaptor-inducing interferon-b (TRIF)-dependent but myeloid differentiation factor 88-independent. The authors also demonstrated that receptor-interacting protein (RIP1) and p38 mitogen-activated protein kinase were required for LPS-induced autophagy. Meanwhile, inhibiting PI3K blocked LPS-induced autophagy. Mechanistically, LPS can promote the incorporation of class III PI3K VPS34 complex containing beclin1 and regulatory subunit p150 into the preautophagosomal membrane and facilitate autophagosome formation. Further results demonstrated that LPS-induced autophagosome could increase mycobacterial colocalization with autophagosomes. Taken together, autophagy and innate immunity were linked together through TLR4-TRIF-mediated pathway.

References:

1.      Kirkegaard, K., et al. 2004. Cellular autophagy: surrender, avoidance and subversion by microorganisms. Nat. Rev. Microbiol. 2:301-314.

2.      Xu, Y., et al. 2007. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27:135-144.