Cell-autonomous immunity by IFN-induced GBPs in animals and plants

Abstract

Inside host cells, guanylate binding proteins (GBPs) rapidly assemble into large antimicrobial defense complexes that combat a wide variety of bacterial pathogens. These massive nanomachines often completely coat targeted microbes where they act as recruitment platforms for downstream effectors capable of direct bactericidal activity. GBP-containing platforms also serve as sensory hubs to activate inflammasome-driven responses in the mammalian cytosol while in plants like Arabidopsis, GBP orthologues may facilitate intranuclear signaling for immunity against invasive phytopathogens. Together, this group of immune GTPases serve as a major defensive repertoire to protect the host cell interior from bacterial colonization across plant and animal kingdoms.

Figure 1.. Evolution of GBPs in plants and animals.

(A) Simple unrooted phylogram of GBPs and GBP-like (GBPL) orthologues across selected animals and plants. Number of family members uncovered from genome NCBI BLAST searches depicted in red font. (B) 3D protein structure prediction (I-TASSER) of Arabidopsis thaliana GBPLs versus crystallized hGBP1 (PDB 1F5N). In addition to the catalytic GTPase domain (GD) and C-terminal helical domain (HD) found in humans, some plant GBPLs also possess long C-terminal extensions that contain intrinsically disordered regions (IDRs). (C) Antibacterial activities of GBPs operate in animals and plants. In IFN-•-induced human HeLa epithelial cells, GBP1 completely coats Salmonella typhimurium or its Salmonella-containing vacuole as shown by live wide-field imaging. 3D-rendered views constructed using Imaris software. Scale bar, 2 •m.

Figure 2.. Antibacterial functions of GBPs in immune and non-immune cells.

Specific GBP family members involved in intrinsic host defense in (A) immune and (B) non-immune cells. Specific assembly of the NADPH oxidase, inflammasome components and IRGB10 as well as the block in F-actin polymerization are depicted. Inflammasome assembly may take place directly on targeted bacteria as indicated by question marks. GBP-interacting partners Galectin-3, p62/SQSTM1 and ATG4B are in grey font with bacterial species targeted by GBP-mediated defense activities boxed in the upper right corner. The Shigella E3 ligase IpaH9.8 responsible for ubiquitinating GBPs followed by proteasomal degradation is also shown. zGBP4, zebrafish GBP4.

Figure 3.. Plant GBPLs in intranuclear immunity.

(A) Intranuclear immunity to bacterial phytopathogens by Arabidopsis GBPLs may operate downstream of cytosolic NLRs as part of the ‘guard” hypothesis or effector-triggered immunity (ETI). (B) Circular dendogram of GBP-like orthologues in various plant hosts. Abbreviations: ZM, Zea mays (maize); OS, Oryza sativa (rice); GM, Glycine max (soybean); CR, Chlamydomonas reinhardtii (algae); PP, Physcomitrella patens (moss). Arabidopsis thaliana (At) GBPLs are highlighted in color. Branch distances from bootstap of 5,000 replicates in maximum likelihood analysis (C) Domain architecture of Arabidopsis and human GBPs showing reconfigured C-termini for AtGBPL1 and AtGBPL3. (D) Nuclear localization of AtGBPL3 shown via stable expression of a GFP-fused construct within A. thaliana roots. FM 4–64 visualizes individual plant cell membranes. Overlay of confocal fluorescence with differential interference contrast microscopy.