β-Catenin promotes host resistance against Pseudomonas aeruginosa keratitis

Chen, Kang; Yin, Lin; Nie, Xinxin; Deng, Qiuchan; Wu, Yongjian; Zhu, Min; Li, Dandan; Li, Meiyu; Wu, Minhao; Huang, Xi

doi:10.1016/j.jinf.2013.07.025

Cited by 34 publications

(44 citation statements)

References 83 publications

(60 reference statements)

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“…Wnt signaling is an evolutionarily conserved pathway that plays a critical role in embryogenesis and cell proliferation and differentiation (64). Additionally, recent studies found that activation of the Wnt signaling pathway regulates the immune response to certain pathogenic bacterial infections by upregulating the expression of anti-inflammatory factors and downregulating the expression of inflammatory factors (65)(66)(67)(68). nkd is linked to Wnt signaling and was originally found to act as an inducible antagonist of Wnt signaling during embryonic development in Drosophila (52).…”

Section: Discussionmentioning

confidence: 99%

Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene ( nkd ) Improves Host Immune Function and Reduces Nosema ceranae Infections

Li¹,

Evans²,

Huang

et al. 2016

Appl Environ Microbiol

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Nosema ceranae is a new and emerging microsporidian parasite of European honey bees, Apis mellifera, that has been implicated in colony losses worldwide. RNA interference (RNAi), a posttranscriptional gene silencing mechanism, has emerged as a potent and specific strategy for controlling infections of parasites and pathogens in honey bees. While previous studies have focused on the silencing of parasite/pathogen virulence factors, we explore here the possibility of silencing a host factor as a mechanism for reducing parasite load. Specifically, we used an RNAi strategy to reduce the expression of a honey bee gene, naked cuticle (nkd), which is a negative regulator of host immune function. Our studies found that nkd mRNA levels in adult bees were upregulated by N. ceranae infection (and thus, the parasite may use this mechanism to suppress host immune function) and that ingestion of double-stranded RNA (dsRNA) specific to nkd efficiently silenced its expression. Furthermore, we found that RNAimediated knockdown of nkd transcripts in Nosema-infected bees resulted in upregulation of the expression of several immune genes (Abaecin, Apidaecin, Defensin-1, and PGRP-S2), reduction of Nosema spore loads, and extension of honey bee life span. The results of our studies clearly indicate that silencing the host nkd gene can activate honey bee immune responses, suppress the reproduction of N. ceranae, and improve the overall health of honey bees. This study represents a novel host-derived therapeutic for honey bee disease treatment that merits further exploration. IMPORTANCEGiven the critical role of honey bees in the pollination of agricultural crops, it is urgent to develop strategies to prevent the colony decline induced by the infection of parasites/pathogens. Targeting parasites and pathogens directly by RNAi has been proven to be useful for controlling infections in honey bees, but little is known about the disease impacts of RNAi silencing of host factors. Here, we demonstrate that knocking down the honey bee immune repressor-encoding nkd gene can suppress the reproduction of N. ceranae and improve the overall health of honey bees, which highlights the potential role of host-derived and RNAi-based therapeutics in controlling the infections in honey bees. The information obtained from this study will have positive implications for honey bee disease management practices. E uropean honey bees, Apis mellifera, play a critical role in the pollination of important crops. However, honey bee populations have suffered high losses in much of the world (1), coincident with an increase in agricultural demand for honey bee pollination (2). Specifically, honey bee colony losses in the United States have been exacerbated since the report of colony collapse disorder (CCD), a syndrome that comprises large-scale, unexplained losses of managed honey bees (3-9). High levels of parasites and pathogens have been linked to the decline of honey bee colonies (10,11).Nosema is a genus of obligate, intracellular microsporidian parasite...

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Section: Discussionmentioning

confidence: 99%

Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene ( nkd ) Improves Host Immune Function and Reduces Nosema ceranae Infections

Li¹,

Evans²,

Huang

et al. 2016

Appl Environ Microbiol

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“…Intracellular bacterial killing was assessed by the use of plate counts as previously described by our group (21,22) and other groups (23). In brief, differentiated THP-1 cells were cultured in a six-well plate and then treated with rapamycin or IL-1␤ or transfected with siRNAs against ATG7 or Beclin1, followed by P. aeruginosa challenge at a multiplicity of infection (MOI) of 25.…”

Section: Materials and Reagentsmentioning

confidence: 99%

Pseudomonas aeruginosa Triggers Macrophage Autophagy To Escape Intracellular Killing by Activation of the NLRP3 Inflammasome

et al. 2016

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Assembly of the inflammasome has recently been identified to be a critical event in the initiation of inflammation. However, its role in bacterial killing remains unclear. Our study demonstrates that Pseudomonas aeruginosa infection induces the assembly of the NLRP3 inflammasome and the sequential secretion of caspase1 and interleukin-1␤ (IL-1␤) in human macrophages. More importantly, activation of the NLRP3 inflammasome reduces the killing of P. aeruginosa in human macrophages, without affecting the generation of antimicrobial peptides, reactive oxygen species, and nitric oxide. In addition, our results demonstrate that P. aeruginosa infection increases the amount of the LC3-II protein and triggers the formation of autophagosomes in human macrophages. The P. aeruginosa-induced autophagy was enhanced by overexpression of NLRP3, ASC, or caspase1 but was reduced by knockdown of these core molecules of the NLRP3 inflammasome. Treatment with IL-1␤ enhanced autophagy in human macrophages. More importantly, IL-1␤ decreased the macrophage-mediated killing of P. aeruginosa, whereas knockdown of ATG7 or Beclin1 restored the IL-1␤-mediated suppression of bacterial killing. Collectively, our study explores a novel mechanism employed by P. aeruginosa to escape from phagocyte killing and may provide a better understanding of the interaction between P. aeruginosa and host immune cells, including macrophages.

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“…Immunofluorescence staining was performed as previously described [28]. RAW264.7 cells or THP-1 macrophages were grown on collagen-precoated coverslips in 24-well plates.…”

Section: Immunofluorescence Staining and Confocal Microscopymentioning

confidence: 99%

β-Catenin promotes host resistance against Pseudomonas aeruginosa keratitis

Cited by 34 publications

References 83 publications

Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene ( nkd ) Improves Host Immune Function and Reduces Nosema ceranae Infections

Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene ( nkd ) Improves Host Immune Function and Reduces Nosema ceranae Infections

Pseudomonas aeruginosa Triggers Macrophage Autophagy To Escape Intracellular Killing by Activation of the NLRP3 Inflammasome

Pseudomonas aeruginosa promotes autophagy to suppress macrophage-mediated bacterial eradication

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