Heat Shock and Genetic Activation of HSF-1 Enhance Immunity to Bacteria

Singh, Varsha; Aballay, Alejandro

doi:10.4161/cc.5.21.3434

Cited by 60 publications

(46 citation statements)

References 34 publications

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“…Genetic or environmental interventions that operate via stress-responsive mechanisms extend both lifespan and pathogen resistance [6], [15], [32], [47], [48]. Our results on H 2 O 2 -induced pathogen resistance (Figure 5B), together with previous analogous heat-shock experiments [7] suggest that mild stresses acting early in adulthood confer resistance against pathogenic stress.…”

Section: Discussionsupporting

confidence: 73%

A Role for SKN-1/Nrf in Pathogen Resistance and Immunosenescence in Caenorhabditis elegans

2012

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A proper immune response ensures survival in a hostile environment and promotes longevity. Recent evidence indicates that innate immunity, beyond antimicrobial effectors, also relies on host-defensive mechanisms. The Caenorhabditis elegans transcription factor SKN-1 regulates xenobiotic and oxidative stress responses and contributes to longevity, however, its role in immune defense is unknown. Here we show that SKN-1 is required for C. elegans pathogen resistance against both Gram-negative Pseudomonas aeruginosa and Gram-positive Enterococcus faecalis bacteria. Exposure to P. aeruginosa leads to SKN-1 accumulation in intestinal nuclei and transcriptional activation of two SKN-1 target genes, gcs-1 and gst-4. Both the Toll/IL-1 Receptor domain protein TIR-1 and the p38 MAPK PMK-1 are required for SKN-1 activation by PA14 exposure. We demonstrate an early onset of immunosenescence with a concomitant age-dependent decline in SKN-1-dependent target gene activation, and a requirement of SKN-1 to enhance pathogen resistance in response to longevity-promoting interventions, such as reduced insulin/IGF-like signaling and preconditioning H2O2 treatment. Finally, we find that wdr-23(RNAi)-mediated constitutive SKN-1 activation results in excessive transcription of target genes, confers oxidative stress tolerance, but impairs pathogen resistance. Our findings identify SKN-1 as a novel regulator of innate immunity, suggests its involvement in immunosenescence and provide an important crosstalk between pathogenic stress signaling and the xenobiotic/oxidative stress response.

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Section: Discussionsupporting

confidence: 73%

A Role for SKN-1/Nrf in Pathogen Resistance and Immunosenescence in Caenorhabditis elegans

2012

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“…Considering the crosstalk between UPR and HSR, and taking into account that some UPR genes are also regulated by HSR, we hypothesized that HSF-1 may modulate C. elegans innate immunity in concert with UPR. Previous studies reported that increased activities of HSF-1, either by overexpression or reducing IIS, lead to an enhanced C. elegans innate immunity [50]. Recently, we found that WCESP acts through IIS pathway to modulate C. elegans lifespan [18].…”

Section: Discussionmentioning

confidence: 71%

Cranberry Extract Standardized for Proanthocyanidins Promotes the Immune Response of Caenorhabditis elegans to Vibrio cholerae through the p38 MAPK Pathway and HSF-1

et al. 2014

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Botanicals are rich in bioactive compounds, and some offer numerous beneficial effects to animal and human health when consumed. It is well known that phytochemicals in cranberries have anti-oxidative and antimicrobial activities. Recently, an increasing body of evidence has demonstrated that cranberry phytochemicals may have potential benefits that promote healthy aging. Here, we use Caenorhabditis elegans as a model to show that water-soluble cranberry extract standardized to 4.0% proanthocyanidins (WCESP), a major component of cranberries, can enhance host innate immunity to resist against Vibrio cholerae (V. cholerae; wild type C6706 (O1 El Tor biotype)) infection. Supplementation of WCESP did not significantly alter the intestinal colonization of V. cholerae, but upregulated the expression of C. elegans innate immune genes, such as clec-46, clec-71, fmo-2, pqn-5 and C23G10.1. Additionally, WCESP treatment did not affect the growth of V. cholerae and expression of the major bacterial virulence genes, and only slightly reduced bacterial colonization within C. elegans intestine. These findings indicate that the major components of WCESP, including proanthocyanidins (PACs), may play an important role in enhancing the host innate immunity. Moreover, we engaged C. elegans mutants and identified that the p38 MAPK signaling, insulin/IGF-1 signaling (IIS), and HSF-1 play pivotal roles in the WCESP-mediated host immune response. Considering the level of conservation between the innate immune pathways of C. elegans and humans, the results of this study suggest that WCESP may also play an immunity-promoting role in higher order organisms.

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“…Taken together, we postulate that protein synthesis inhibition mediated by SidI plays a role in induction of the host stress response, possibly to provide a cellular environment more conducive for bacterial replication. The induction of a host heat stress response has been documented in infections caused by a variety of pathogens and its roles in infections can be either beneficial or detrimental to the infecting agents (Singh and Aballay, 2006; Glotzer et al ., 2000). Clearly, different pathogens have evolved different strategies to modulate this cellular pathway.…”

Section: Discussionmentioning

confidence: 99%

Targeting eEF1A by aLegionella pneumophilaeffector leads to inhibition of protein synthesis and induction of host stress response

Shen

Banga

Liu

et al. 2009

Cellular Microbiology

128

149

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SummaryThe Legionella pneumophila Dot/Icm type IV secretion system is essential for the biogenesis of a phagosome that supports bacterial multiplication, most likely via the functions of its protein substrates. Recent studies indicate that fundamental cellular processes, such as vesicle trafficking, stress response, autophagy and cell death, are modulated by these effectors. However, how each translocated protein contributes to the modulation of these pathways is largely unknown. In a screen to search substrates of the Dot/Icm transporter that can cause host cell death, we identified a gene whose product is lethal to yeast and mammalian cells. We demonstrate that this protein, called SidI, is a substrate of the Dot/Icm type IV protein transporter that targets the host protein translation process. Our results indicate that SidI specifically interacts with eEF1A and eEF1Bg, two components of the eukaryotic protein translation elongation machinery and such interactions leads to inhibition of host protein synthesis. Furthermore, we have isolated two SidI substitution mutants that retain the target binding activity but have lost toxicity to eukaryotic cells, suggesting potential biochemical effect of SidI on eEF1A and eEF1Bg. We also show that infection by L. pneumophila leads to eEF1A-mediated activation of the heat shock regulatory protein HSF1 in a virulence-dependent manner and deletion of sidI affects such activation.Moreover, similar response occurred in cells transiently transfected to express SidI. Thus, inhibition of host protein synthesis by specific effectors contributes to the induction of stress response in L. pneumophila-infected cells.

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Heat Shock and Genetic Activation of HSF-1 Enhance Immunity to Bacteria

Cited by 60 publications

References 34 publications

A Role for SKN-1/Nrf in Pathogen Resistance and Immunosenescence in Caenorhabditis elegans

A Role for SKN-1/Nrf in Pathogen Resistance and Immunosenescence in Caenorhabditis elegans

Cranberry Extract Standardized for Proanthocyanidins Promotes the Immune Response of Caenorhabditis elegans to Vibrio cholerae through the p38 MAPK Pathway and HSF-1

Targeting eEF1A by aLegionella pneumophilaeffector leads to inhibition of protein synthesis and induction of host stress response

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