A Batf3/Nlrp3/IL-18 Axis Promotes Natural Killer Cell IL-10 Production during Listeria monocytogenes Infection

Clark, Sarah E.; Schmidt, Rebecca L.; McDermott, Daniel S.; Lenz, Laurel

doi:10.1016/j.celrep.2018.04.106

Cited by 34 publications

(35 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AIM2 expression requires type I IFN signalling, consistent with which, L. monocytogenes ‐induced inflammasome activation is severely reduced in type I IFN‐receptor deficient ( Ifnar −/− ) macrophages. L. monocytogenes is a poor activator of NLRC4 (Sauer et al, ; Warren et al, ; Sauer et al, ), but can activate NLRP6, caspase‐11 (Hara et al, ) and NLRP1B (Neiman‐Zenevich et al, ) in mouse macrophages, and NLRP3 in mouse bone‐marrow derived DCs (Clark, Schmidt, McDermott, & Lenz, ). Most L. monocytogenes strains turn down flagellin expression at 37°C and thus evade detection by TLR5 and the NAIP5‐NLRC4 pathway (Theisen & Sauer, ).…”

Section: Monocytogenes Benefits From Inflammasome Activationmentioning

confidence: 99%

“…L. monocytogenes is a poor activator of NLRC4 (Sauer et al, 2010;Warren et al, 2010;Sauer et al, 2011), but can activate NLRP6, caspase-11 (Hara et al, 2018) andNLRP1B (Neiman-Zenevich et al, 2017) in mouse macrophages, and NLRP3 in mouse bone-marrow derived DCs (Clark, Schmidt, McDermott, & Lenz, 2018). Most L. monocytogenes strains turn down flagellin expression at 37 C and thus evade detection by TLR5 and the NAIP5-NLRC4 pathway (Theisen & Sauer, 2016).…”

Section: Shigella -Inflammasome Interactions Are Cell-type Specificmentioning

confidence: 99%

“…Early in vivo studies on L. monocytogenes pointed towards a protective role of inflammasome-related genes (Hirsch, Irikura, Paul, & Hirsh, 1996;Labow et al, 1997;Tsuji et al, 2004); however, these studies were carried out in mice with a mixed C57BL/6 and 129/S background which also carry an inactivating passenger mutation in Casp11. More recent studies suggest that loss of Il18, Nlrp3 or Asc increases resistance to L. monocytogenes, and loss of Casp1/11 −/− does not markedly affect survival or adaptive immune responses (Lochner et al, 2008;Sauer et al, 2011;Tsuchiya et al, 2014;Clark et al, 2018). Intriguingly, Nlrp6 −/− and Casp11 −/− mice, which would not recognise Listeria LTA, are also more resistant to L. monocytogenes infection (Hara et al, 2018).…”

Section: Shigella -Inflammasome Interactions Are Cell-type Specificmentioning

confidence: 99%

See 2 more Smart Citations

Vying for the control of inflammasomes: The cytosolic frontier of enteric bacterial pathogen–host interactions

Sanchez‐Garrido

Slater

Clements

et al. 2020

Cellular Microbiology

View full text Add to dashboard Cite

Enteric pathogen–host interactions occur at multiple interfaces, including the intestinal epithelium and deeper organs of the immune system. Microbial ligands and activities are detected by host sensors that elicit a range of immune responses. Membrane‐bound toll‐like receptors and cytosolic inflammasome pathways are key signal transducers that trigger the production of pro‐inflammatory molecules, such as cytokines and chemokines, and regulate cell death in response to infection. In recent years, the inflammasomes have emerged as a key frontier in the tussle between bacterial pathogens and the host. Inflammasomes are complexes that activate caspase‐1 and are regulated by related caspases, such as caspase‐11, ‐4, ‐5 and ‐8. Importantly, enteric bacterial pathogens can actively engage or evade inflammasome signalling systems. Extracellular, vacuolar and cytosolic bacteria have developed divergent strategies to subvert inflammasomes. While some pathogens take advantage of inflammasome activation (e.g. Listeria monocytogenes, Helicobacter pylori), others (e.g. E. coli, Salmonella, Shigella, Yersinia sp.) deploy a range of virulence factors, mainly type 3 secretion system effectors, that subvert or inhibit inflammasomes. In this review we focus on inflammasome pathways and their immune functions, and discuss how enteric bacterial pathogens interact with them. These studies have not only shed light on inflammasome‐mediated immunity, but also the exciting area of mammalian cytosolic immune surveillance.

show abstract

Section: Monocytogenes Benefits From Inflammasome Activationmentioning

confidence: 99%

Section: Shigella -Inflammasome Interactions Are Cell-type Specificmentioning

confidence: 99%

Section: Shigella -Inflammasome Interactions Are Cell-type Specificmentioning

confidence: 99%

See 1 more Smart Citation

Vying for the control of inflammasomes: The cytosolic frontier of enteric bacterial pathogen–host interactions

Sanchez‐Garrido

Slater

Clements

et al. 2020

Cellular Microbiology

View full text Add to dashboard Cite

show abstract

“…However, under normal physiological conditions, Batf3 -dependent CD8α + DC appear to play a central role in the activation of CD8 T cells, which has also been corroborated by in vitro studies showing that CD8α + DC are more effective than CD11b + DC at eliciting CD8 T cell responses to Lm [ 26 ]. In addition to their role in transporting Lm to the T cell zone and activating CD8 T cells, a new study demonstrated that Batf3 -dependent CD8α + DC are a vital source of IL-18, which subsequently licenses Natural Killer (NK) cells to produce IL-10 [ 27 ]. As NK cell-derived IL-10 promotes susceptibility to Lm infection [ 28 ], this new study provides an additional mechanism that contributes to the resistance of mice deficient in Batf3 -dependent CD8α + DC to Lm infection.…”

Section: Listeria Monocytogenes (Lm) Acquisitiomentioning

confidence: 99%

Listeria Monocytogenes: A Model Pathogen Continues to Refine Our Knowledge of the CD8 T Cell Response

2018

View full text Add to dashboard Cite

Listeria monocytogenes (Lm) infection induces robust CD8 T cell responses, which play a critical role in resolving Lm during primary infection and provide protective immunity to re-infections. Comprehensive studies have been conducted to delineate the CD8 T cell response after Lm infection. In this review, the generation of the CD8 T cell response to Lm infection will be discussed. The role of dendritic cell subsets in acquiring and presenting Lm antigens to CD8 T cells and the events that occur during T cell priming and activation will be addressed. CD8 T cell expansion, differentiation and contraction as well as the signals that regulate these processes during Lm infection will be explored. Finally, the formation of memory CD8 T cell subsets in the circulation and in the intestine will be analyzed. Recently, the study of CD8 T cell responses to Lm infection has begun to shift focus from the intravenous infection model to a natural oral infection model as the humanized mouse and murinized Lm have become readily available. Recent findings in the generation of CD8 T cell responses to oral infection using murinized Lm will be explored throughout the review. Finally, CD8 T cell-mediated protective immunity against Lm infection and the use of Lm as a vaccine vector for cancer immunotherapy will be highlighted. Overall, this review will provide detailed knowledge on the biology of CD8 T cell responses after Lm infection that may shed light on improving rational vaccine design.

show abstract

“…Infection of wildtype mice with L . monocytogenes results in high levels of serum IL-10 3–4 days post infection [ 11 , 12 ]. Mice lacking IL-10 clear L .…”

Section: Introductionmentioning

confidence: 99%

TLR2 and endosomal TLR-mediated secretion of IL-10 and immune suppression in response to phagosome-confined Listeria monocytogenes

et al. 2020

View full text Add to dashboard Cite

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from phagosomes and induces a robust adaptive immune response in mice, while mutants unable to escape phagosomes fail to induce a robust adaptive immune response and suppress the immunity to wildtype bacteria when co-administered. The capacity to suppress immunity can be reversed by blocking IL-10. In this study, we sought to understand the host receptors that lead to secretion of IL-10 in response to phagosome-confined L . monocytogenes (Δ hly ), with the ultimate goal of generating strains that fail to induce IL-10. We conducted a transposon screen to identify Δ hly L . monocytogenes mutants that induced significantly more or less IL-10 secretion in bone marrow-derived macrophages (BMMs). A transposon insertion in lgt , which encodes phosphatidylglycerol-prolipoprotein diacylglyceryl transferase and is essential for the formation of lipoproteins, induced significantly reduced IL-10 secretion. Mutants with transposon insertions in pgdA and oatA , which encode peptidoglycan N-acetylglucosamine deacetylase and O-acetyltransferase, are sensitive to lysozyme and induced enhanced IL-10 secretion. A Δ hly Δ pgdA Δ oatA strain was killed in BMMs and induced enhanced IL-10 secretion that was dependent on Unc93b1, a trafficking molecule required for signaling of nucleic acid-sensing TLRs. These data revealed that nucleic acids released by bacteriolysis triggered endosomal TLR-mediated IL-10 secretion. Secretion of IL-10 in response to infection with the parental strain was mostly TLR2-dependent, while IL-10 secretion in response to lysozyme-sensitive strains was dependent on TLR2 and Unc93b1. In mice, the IL-10 response to vacuole-confined L . monocytogenes was also dependent on TLR2 and Unc93b1. Co-administration of Δ hly and Δ actA resulted in suppressed immunity in WT mice, but not in mice with mutations in Unc93b1. These data revealed that secretion of IL-10 in response to L . monocytogenes infection in vitro is mostly TLR2-dependent and immune suppression by phagosome-confined bacteria in vivo is mostly dependent on endosomal TLRs.

show abstract

A Batf3/Nlrp3/IL-18 Axis Promotes Natural Killer Cell IL-10 Production during Listeria monocytogenes Infection

Cited by 34 publications

References 55 publications

Vying for the control of inflammasomes: The cytosolic frontier of enteric bacterial pathogen–host interactions

Vying for the control of inflammasomes: The cytosolic frontier of enteric bacterial pathogen–host interactions

Listeria Monocytogenes: A Model Pathogen Continues to Refine Our Knowledge of the CD8 T Cell Response

TLR2 and endosomal TLR-mediated secretion of IL-10 and immune suppression in response to phagosome-confined Listeria monocytogenes

Contact Info

Product

Resources

About