Nucleic Acid Sensing in Mammals and Plants: Facts and Caveats

Trial Watch: experimental TLR7/TLR8 agonists for oncological indications

“…[1][2][3][4][5][6][7][8] Nonetheless, attention on alternative immunotherapeutic approaches has remained high, at least in part reflecting: (1) the relatively small fraction of patients responding to ICBs employed as single agents; [9][10][11] (2) the considerable side effects associated with some ICBs, especially when combined with each other; [12][13][14][15] and (3) the economic burden of ICB-based immunotherapy. 16,17 Besides monoclonal antibodies that operate as agonists of co-stimulatory receptors on immune effector cells, [18][19][20] such immunotherapeutic agents include small molecules that trigger Toll-like receptor (TLR) signaling, [21][22][23][24][25][26][27][28][29] de facto providing antigen-presenting cells (APCs) such as dendritic cells (DCs) [30][31][32] with adjuvant-like, maturation signals that support the initiation of anticancer immunity (rather than tolerance). 22,[33][34][35][36][37][38] TLRs are evolutionary conserved pattern recognition receptors (PRRs) localized at the cell surface or in endosomal compartments, and act as key mediators of innate immunity.…”

“…22,[33][34][35][36][37][38] TLRs are evolutionary conserved pattern recognition receptors (PRRs) localized at the cell surface or in endosomal compartments, and act as key mediators of innate immunity. 26,[39][40][41][42][43] As a family, TLRs play a crucial role in ensuring a first line of defense against pathogens, largely based on their ability to respond to conserved microbial structures commonly referred to as microbe-associated molecular patterns (MAMPs) by initiating the secretion of bioactive factors including numerous cytokines. 40,[44][45][46][47] Alongside this pristine antimicrobial function, TLRs also respond to a number of endogenous cues commonly referred to damage-associated molecular patterns (DAMPs), which are critical for the detection of cell stress and death as immunogenic in sterile conditions.…”

Breaking Bad News: Dynamic Molecular Mechanisms of Wound Response in Plants

“…Briefly, human HMGB1 binds in the nucleus to DNA, facilitating nucleosome formation and transcription factor binding (Thomas and Travers, 2001;Lotze and Tracey, 2005). Upon its release outside the cell, it can be recognized by various cell surface receptors (Heil and Vega-Muñoz, 2019). In metazoans, HMGB1 facilitates tissue repair and healing by promoting the switch of macrophages to a tissue-healing phenotype (Bianchi et al, 2017).…”

“…Intriguingly, the ability of non-selfderived DNA to trigger an immune response is lower or undetectable than the ones induced by self-derived DNA (Duran-Flores and Heil, 2018), suggesting a species-specific perception mechanism that discriminates self-derived DNA from non-self DNA. To date, no DNA receptor has been identified in plant cells, and none of the receptors that are known from mammals discriminate between self and non-self DNA (Heil and Vega-Muñoz, 2019). Extracellular DNA present on plant root tips is required for defense against a necrotrophic fungus (Wen et al, 2009), and it was recently reported that secreted DNases by a fungal pathogen (Cochliobolus heterostrophus) and a herbivore (Laodelphax striatellus) serve as effectors that suppress DNA-dependent plant immunity, reinforcing the biological relevance of DNA as a DAMP in plants (Huang et al, 2019).…”

In SilicoPhylogenetic and Structural Analyses of Plant Endogenous Danger Signaling Molecules upon Stress

“…In plant cells, there is emerging evidence of the connection between DAMPs and the DNA damage response (DDR), as nucleic acid recognition represents a fundamental step in host defense. Plants have been documented to perceive both extracellular DNA and RNA [12–14]. Toll-like receptors (TLRs) play a central role in the preferential recognition and binding of extracellular DNA in animals [15–19].…”