The Potential Role of Trained Immunity in Autoimmune and Autoinflammatory Disorders

Arts, Rob J. W.; Joosten, Leo A. B.; Netea, Mihai G.

doi:10.3389/fimmu.2018.00298

Cited by 140 publications

(136 citation statements)

References 246 publications

(220 reference statements)

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“…27 It is therefore essential to identify the modulatory mechanisms that control the inappropriate induction of trained immunity, and we hypothesized that TLR10 may have such a regulatory role. 27 It is therefore essential to identify the modulatory mechanisms that control the inappropriate induction of trained immunity, and we hypothesized that TLR10 may have such a regulatory role.…”

Section: Discussionmentioning

confidence: 99%

“…The importance of trained immunity in autoimmune and inflammatory diseases is becoming increasingly clear. 27 It is therefore essential to identify the modulatory mechanisms that control the inappropriate induction of trained immunity, and we hypothesized that TLR10 may have such a regulatory role. TLR10 mRNA as well as TLR10 protein expression is not altered during the induction of b-glucanand BCG-induced trained immunity in vitro.…”

Section: Discussionmentioning

confidence: 99%

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The role of Toll‐like receptor 10 in modulation of trained immunity

et al. 2019

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Toll-like receptor 10 (TLR10) is the only member of the human Toll-like receptor family with an inhibitory function on the induction of innate immune responses and inflammation. However, its role in the modulation of trained immunity (innate immune memory) is unknown. In the present study, we assessed whether TLR10 modulates the induction of trained immunity induced by b-glucan or bacillus Calmette-Gu erin (BCG). Interleukin 10 receptor antagonist production was increased upon activation of TLR10 ex vivo after BCG vaccination, and TLR10 protein expression on monocytes was increased after BCG vaccination, whereas anti-TLR10 antibodies did not significantly modulate b-glucan or BCG-induced trained immunity in vitro. A known immunomodulatory TLR10 missense single-nucleotide polymorphism (rs11096957) influenced trained immunity responses by b-glucan or BCG in vitro. However, the in vivo induction of trained immunity by BCG vaccination was not influenced by TLR10 polymorphisms. In conclusion, TLR10 has a limited, non-essential impact on the induction of trained immunity in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The role of Toll‐like receptor 10 in modulation of trained immunity

et al. 2019

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“…Moreover, it is tempting to speculate that innate immune memory may help to explain the increasing S. sonnei burden in regions where improved water sanitisation has eliminated P. shigelloides and subsequently reduced cross-immunisation against S. sonnei O-Ag [16,17]. Consistent with this, the incidence of S. sonnei infection is mostly observed in very young children (<5 years old) [34][35][36][37][38], an age group where trained innate immunity has been shown to play an important protective role [32,33,[39][40][41].…”

Section: Discussionmentioning

confidence: 87%

Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence

et al. 2019

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Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo. Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that Oantigen enables S. sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in developing countries.

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“…Moreover, it is tempting to speculate that innate immune memory may help to explain the increasing S. sonnei burden in regions where improved water sanitisation has eliminated P. shigelloides and subsequently reduced cross-immunisation against S. sonnei O-Ag [15, 16]. Consistent with this, the incidence of S. sonnei infection is mostly observed in very young children (<5 years old) [33–37], an age group where trained innate immunity has been shown to play an important protective role [31,32, 38–40].…”

Section: Discussionmentioning

confidence: 96%

Shigella sonneiinfection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence

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et al. 2019

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42 Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the 43 closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The 44 underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) 45 model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo. 46 Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence 47 depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show 48 in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can 49 mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S. 50 sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical 51 inhibition or promotion of phagolysosome maturation respectively decreases and increases 52 neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal 3 53 dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-54 dependent manner, indicating that exposure to O-antigen can train the innate immune system 55 against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic 56 target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in 57 developing countries. 58 59 60 Author Summary 61 Shigella sonnei is predominantly responsible for dysentery in developed countries, and is 62 replacing Shigella flexneri in areas undergoing economic development and improvements in 63 water quality. Using Shigella infection of zebrafish (in vivo) and human neutrophils (in vitro), 64 we discover that S. sonnei is more virulent than S. flexneri because of neutrophil tolerance 65 mediated by its O-antigen oligosaccharide acquired from the environmental bacteria 66 Plesiomonas shigelloides. To inspire new approaches for S. sonnei control, we show that 67 increased phagolysosomal acidification or innate immune training can promote S. sonnei 68 clearance by neutrophils in vivo. These findings have major implications for our evolutionary 69 understanding of Shigella, and may explain why exposure to P. shigelloides in low and middle-70 income countries (LMICs) can protect against dysentery incidence. 71 72 73 4 80 has been a valuable discovery tool in the field of innate immunity, helping to illuminate the role 81 of neutrophil extracellular traps (NETs) [5], nucleotide-binding oligomerisation domain (NOD)-82 like receptors (NLRs) [6], bacterial autophagy [7], interferon-inducible guanylate-binding 83 proteins (GBPs) [8,9] and septin-mediated cell-autonomous immunity [10,11] in host 84 defence. 85 86 The genus Shigella comprises four different species (S. flexneri, S. sonnei, S. boydii, S. 87 dysenteriae), although DNA sequencing suggests they evolved from convergent evolution of 88 different founders [12]. The most recent strains of S. flexne...

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The Potential Role of Trained Immunity in Autoimmune and Autoinflammatory Disorders

Cited by 140 publications

References 246 publications

The role of Toll‐like receptor 10 in modulation of trained immunity

The role of Toll‐like receptor 10 in modulation of trained immunity

Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence

Shigella sonneiinfection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence

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