Review
Golgi Apparatus: An Emerging Platform for Innate Immunity

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Highlights

  • The Golgi apparatus not only functions as an inert sorting organelle but also acts as a signaling platform to facilitate innate immunity.

  • Golgi dispersion acts as a crucial event to initiate NLRP3 inflammasome assembly, and the interface between the Golgi, ER, and mitochondria functions as an important hub for NLRP3 inflammasome activation.

  • ER-to-Golgi trafficking of stimulator of interferon genes (STING) is required for interferon (IFN)-I production and autophagosome formation in response to cytosolic DNA or DNA viruses.

  • The Golgi apparatus acts as the platform for TANK binding kinase 1 (TBK1) activation after Toll-like receptor (TLR)3 or retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) activation.

  • Golgi-localized IFN-inducible GTPases target intracellular pathogens either at the Golgi apparatus or after moving to other cellular compartments.

  • A number of microorganisms use several virulence factors to counteract host defense by targeting the Golgi apparatus or Golgi-associated proteins.

The Golgi apparatus serves as a receiving station where proteins from the endoplasmic reticulum (ER) are further processed before being sent to other cellular compartments. In addition to its well-appreciated roles in vesicular trafficking and protein/lipid secretion, recent studies have demonstrated that the Golgi acts as a signaling platform to facilitate multiple innate immune pathways. Moreover, the membranous networks that connect the Golgi with the ER, mitochondria, endosomes, and autophagosomes provide convenient access to innate immune signal transduction and subsequent effector responses. Here, we review the emerging knowledge about the roles of the Golgi in the initiation and activation of innate immune signaling. Moreover, microbial hijacking strategies that inhibit Golgi-associated innate immune responses will also be discussed.

Section snippets

Golgi in Innate Immunity: Not Only a Sorting Organelle but Also a Signaling Platform

The Golgi apparatus, also known as the Golgi complex/body, or simply the Golgi, is a membrane-bound organelle in eukaryotic cells that is made up of a series of flat sacs called cisternae. As a polarized organelle, the cisternae of the Golgi stacks are divided into three functionally distinct compartments: cis, medial, and trans cisternae, which form the cis-Golgi network (CGN) and the trans-Golgi network (TGN) at the cis and trans faces of the Golgi, respectively [1]. The CGN receives proteins

Golgi Apparatus and NLRP3 Inflammasome

Several members of intracellular NLRs initiate the assembly of inflammasomes that promote IL-1β and IL-18 secretion and induce pyroptosis [10]. Unlike other inflammasomes, which are triggered by a limited number of pathogenic molecules, the NLRP3 inflammasome is activated not only by microbial molecules (such as viral RNA and nigericin) but also by numerous environmental irritants (such as asbestos and silica) and endogenous metabolic products (such as high glucose, monosodium urate crystals,

Golgi Apparatus and cGAS–STING Signaling

Cyclic GMP–AMP synthase (cGAS) is a well-known innate immune receptor that directly recognizes cytosolic double-stranded DNA (dsDNA) and induces the production of the second messenger cyclic GMP–AMP (cGAMP) [23]. cGAMP binds to and activates the adaptor protein stimulator of interferon genes (STING), which in turn activates TANK binding kinase 1 (TBK1) and IκB kinase (IKK), leading to the production of type I interferon (IFN-I) and other inflammatory cytokines through the transcription factors

Golgi Apparatus and TLR/RLR Signaling

In addition to dsDNA-induced cGAS-STING signaling, microbial double-stranded RNA (dsRNA) also initiates the innate immune response though activation of TLR3 and RLR signaling [37]. Upon activation, endosomal TLR3 recruits the adapter TIR-domain-containing adaptor inducing IFNβ (TRIF), while cytoplasmic RLRs, including RIG-I and melanoma differentiation-associated protein 5 (MDA5), recruit and activate mitochondrial antiviral-signaling protein (MAVS). Although the downstream adaptors differ

Golgi Apparatus and IFN-Inducible GTPases

As mentioned above, the activation of multiple PRRs can lead to the production of IFN-I, which exerts a strong antimicrobial effect through the upregulation of numerous IFN-stimulated genes (ISGs). Prominent among the ISGs is a superfamily of interferon-inducible GTPases [51]. Two members of the IFN-inducible GTPases, guanylate-binding protein (GBP)5 and immunity-related GTPase family M (IRGM), are constitutively located at the Golgi apparatus [52., 53., 54.]. Activation of these proteins not

Microbial Hijacking Strategies That Target the Golgi-Associated Innate Immune Responses

Given the importance of the Golgi apparatus in orchestrating innate immune responses, it is not surprising that several pathogenic microorganisms have evolved multiple strategies to antagonize host defense by targeting the Golgi apparatus or Golgi-associated proteins (Table 1).

Non-LEE-encoded effector A (NleA) is a type three secretion system (T3SS) effector that is produced by enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC), as well as Citrobacter rodentium [66].

Concluding Remarks and Future Perspectives

Although its existence had long been questioned since its discovery in 1898, the Golgi is now regarded as the central organelle that organizes vesicular trafficking and protein/lipid transport. Emerging studies have suggested that the Golgi apparatus not only facilitates the processing and transport of proteins/lipids but also functions as a signaling platform for innate immune signaling and subsequent effector responses. In this review, we summarize the roles of the Golgi apparatus in the

Acknowledgements

This work was supported by the National Natural Science Foundation of China (31700777), the China Postdoctoral Science Foundation (BH2070000094), the First Affiliated Hospital of Bengbu Medical College Science Fund for Outstanding Young Scholars (2019byyfyyq05), the Fundamental Research Funds for the Central Universities (WK2070000149 and WK2070080004), and the New Medicine Fund of University of Science and Technology of China (WK2070000170).

Glossary

ADP ribosylation factors (ARFs)
a family of small GTPases that comprise six highly conserved members in mammals (ARF1–ARF6). Similar to other GTP-binding proteins, ARFs cycle between their inactive GDP-bound form and active GTP-bound form. Activation of ARFs regulates vesicular trafficking and actin cytoskeleton remodeling through the recruitment of diverse effectors.
Coat protein complex II (COPII)
a protein complex that is responsible for creating small vesicles and mediating protein transport

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