Designated autophagyrelated genes (ATGs) proteins [1]. See Figure 1 for a brief outline of the different stages in autophagosome formation.Several key molecular events have emerged from the study of starvation induced autophagy. The mTOR complex 1 (mTORC1) regulator is a major sensor of the energy and nutrient status of the cell [12]. Upon activation, mTORC1 phosphorylates ATG13 preventing it from entering the UNC-51 like serine/threonine kinase complex (ULK1 kinase complex). This blocks autophagy. Inhibition of mTORC1 leads to the activation of the ULK1 kinase complex. This links upstream signals to the coreScientifica autophagy machinery as Beclin-1 is a ULK1 substrate. The PtdIns3 P kinase VPS34/Beclin-1/ATG14L complex can then funnel signals to two downstream conjugation systems: ATG5/ATG12/ATG16L1 and ATG7/ATG3/ATG8-LC3 (microtubule-associated light chain 3, GABARAP) [13]. The former adds a phosphatidylethanolamine group to the carboxyl terminus of ATG8 paralogs. This results in lipid conjugation of LC3 into phagophore membrane as LC3-II and is useful as a mammalian autophagic marker. Consequently, ATG8 along with additional factors promotes the elongation and closure of the phagophore, thereby forming the double membrane autophagosome. After that, the autophagosomes can fuse with lysosomes, gaining the capacity to digest their contents by the acquisition of lysosomal hydrolytic enzymes [14]. The fusion is mediated by the translocation of the SNARE protein syntaxin 17 to the outer membrane of autophagosomes [15]. We refer the reader to other comprehensive reviews covering the complex and dynamic initiation mechanisms of autophagy [1, 6, 91].3 constitute one subgroup of PRRs, are a type I transmembrane protein. Structurally TLRs are composed of extracellular portion, which contains leucine-rich repeats responsible for the recognition of PAMPs; the transmembrane domain; and the intracellular Toll/interleukin-1 (IL-1) receptor (TIR) domains, which mediate downstream signaling [27]. To date, 13 TLRs have been identified in mice and 10 in humans. TLRs are positioned either at the cell surface or on the lumen of intracellular vesicles. TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are localized on the plasma membrane and recognize lipids, lipoproteins, and proteins. TLR3, TLR7, TLR8, and TLR9 are localized in intracellular vesicles such as the endoplasmic reticulum (ER), endosomes, lysosomes, and endolysosomes and they detect microbial nucleic acids [27]. TLR2 recognizes lipopeptides, peptidoglycan, lipoteichoic acid, and zymosan derived from pathogens. In addition, TLR2 forms heterodimers with TLR1 and TLR6.Taurochenodeoxycholic acid Such dimerization provides specificity for the detection of certain lipoproteins.M‑89 TLR4 detects lipopolysaccharide (LPS), a major bacterial signature molecule found on the outer membrane of Gram-negative bacteria.PMID:23664186 TLR5 recognizes the flagellin protein, a major component of bacterial flagella. TLR3 detects double-stranded RNA (dsRNA) of RNA viruses and a synthetic analog polyinosinicpolycytidylic acid (poly(I:C)). TLR7 and human TLR8 recognize single-stranded RNA of RNA viruses and imidazoquinoline derivatives such as imiquimod and resiquimod (R848) and guanine analogs. TLR9 recognizes unmethylated 2 -deoxyribo(cytidine-phosphate-guanosine) (CpGs) DNA motifs that are frequently present in viral DNA. TLR10 ligand is still unknown. The binding of PAMPs to TLRs initiates innate immune response and helps prime antigen-specific adaptive immunit.