Interleukin-1α released from HSV-1-infected keratinocytes acts as a functional alarmin in the skin

Milora, Katelynn A.; Miller, Samantha L.; Sanmiguel, Julio; Jensen, Liselotte E.

doi:10.1038/ncomms6230

Cited by 43 publications

(55 citation statements)

References 48 publications

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“…The observation that hypervirulent fungal strains and isolates drive excessive cell death, lung damage, and IL-1␣-dependent inflammation appears to be conserved across numerous types of mucosal pathogens (33,(65)(66)(67)(68)(69)(70). Highly virulent Pseudomonas aeruginosa isolates express a cytotoxin, ExoU, that has been found to induce necrosis and epithelial damage (65).…”

Section: Discussionmentioning

confidence: 99%

Interleukin 1α Is Critical for Resistance against Highly Virulent Aspergillus fumigatus Isolates

et al. 2017

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Heterogeneity among Aspergillus fumigatus isolates results in unique virulence potential and inflammatory responses. How these isolates drive specific immune responses and how this affects fungally induced lung damage and disease outcome are unresolved. We demonstrate that the highly virulent CEA10 strain is able to rapidly germinate within the immunocompetent lung environment, inducing greater lung damage, vascular leakage, and interleukin 1␣ (IL-1␣) release than the low-virulence Af293 strain, which germinates with a lower frequency in this environment. Importantly, the clearance of CEA10 was consequently dependent on IL-1␣, in contrast to Af293. The release of IL-1␣ occurred by a caspase 1/11-and P2XR7-independent mechanism but was dependent on calpain activity. Our finding that early fungal conidium germination drives greater lung damage and IL-1␣-dependent inflammation is supported by three independent experimental lines. First, pregermination of Af293 prior to in vivo challenge drives greater lung damage and an IL-1␣-dependent neutrophil response. Second, the more virulent EVOL20 strain, derived from Af293, is able to germinate in the airways, leading to enhanced lung damage and IL-1␣-dependent inflammation and fungal clearance. Third, primary environmental A. fumigatus isolates that rapidly germinate under airway conditions follow the same trend toward IL-1␣ dependency. Our data support the hypothesis that A. fumigatus phenotypic variation significantly contributes to disease outcomes.

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Section: Discussionmentioning

confidence: 99%

Interleukin 1α Is Critical for Resistance against Highly Virulent Aspergillus fumigatus Isolates

et al. 2017

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“…In light of the IL-36 induction by PAMPs (above), this cytokine induction suggests an important role in orchestrating the positioning of immune cells at sites of infection, as previously only demonstrated for IL-1 signaling (97,98). The first in vivo evidence for a role of the IL-36s in leukocyte recruitment came from studies using IL36a transgenic mice.…”

Section: Role In Leukocyte Recruitmentmentioning

confidence: 99%

“…Hence, IL-1a has been proposed as an evolutionary adaptation of the host to counteract the anti-inflammatory activities of HSV-1 (Fig. 4B) to ensure initiation of appropriate immune responses (97). It is conceivable that IL-33 can act in a similar manner.…”

Section: Viral Immune Evasion and Potential Counteraction By Il-36mentioning

confidence: 99%

“…Despite the evasion mechanisms deployed by HSV-1, IL-1a is released from HSV-1-infected keratinocytes in vitro in a manner that is independent of caspase-1 and in vivo promotes inflammation at infected sites in the skin (97). Hence, IL-1a has been proposed as an evolutionary adaptation of the host to counteract the anti-inflammatory activities of HSV-1 (Fig.…”

Section: Viral Immune Evasion and Potential Counteraction By Il-36mentioning

confidence: 99%

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Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling

Jensen

2017

Sci. Signal.

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Pathogens deploy immune evasion strategies to successfully establish infections within their hosts. Naturally, the host responds by acquiring mechanisms to counter these strategies. There is increasing evidence that the three interleukin-36 (IL-36) cytokines, IL-36a, IL-36b and IL-36g, play important roles in host immunity. With a focus on the skin as a target for microbial and viral invasion, the current knowledge of IL-36 functions is reviewed. Furthermore, the hypothesis that the IL-36s have evolved to counteract virulence factors is presented using viruses as an example. The IL-36s are related to IL-1a, IL-1b, IL-18, and IL-33. Numerous viruses affecting the skin have developed immune evasion strategies that neutralize IL-1a, IL-1b, or IL-18 signaling or combinations of these pathways. Through small differences in activation mechanisms and receptor utilization, it is possible that IL-36 signaling may proceed unhindered in the presence of these viral inhibitors. Thus, one physiological function of the IL-36s may be to counteract microbial immune evasion.

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“…Interleukin-1alpha (IL-1alpha) is one of the many cytokines represented by the Interleukin-1 family. High levels of IL-1alpha are found in keratinocytes and necrotic cells (8). IL-1alpha, along with its agonist (IL-1beta), is released during programmed cell death; however only IL-1alpha plays a role in malignant cell death activation (9).…”

Section: Discussionmentioning

confidence: 99%

Effect of Selenium Supplementation on Proteomic Serum Biomarkers in Elderly Men

et al. 2015

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Objectives: To determine the effect of selenium supplementation on the human proteomic profile. Design: Serum samples were collected in this pilot study from a randomized placebo controlled Phase 2 Watchful Waiting (WW) clinical trial. Setting: Subjects were followed every three months for up to five years at the University of Arizona Prostate Cancer Prevention Program Clinic. Participants: One hundred and forty men (age < 85 years) had biopsy-proven prostate cancer, a Gleason sum score less than eight, no metastatic cancer, and no prior treatment for prostate cancer. Intervention: As part of the WW trial, men were randomized to placebo, selenium 200 μg/day or selenium 800 μg/day. For the purpose of the current study, 40 subjects enrolled in the WW study (20 from the placebo group and 20 from Se 800 μg/day group) were selected. Measurements: Baseline serum samples were collected at each follow-up visit and stored at -80 degrees Celsius. A multiplexed proteomic panel investigated changes in 120 proteins markers simultaneously. Results: Thirteen proteins (Apolipoprotein J, IL-10, IL-1 alpha, MMP-3, IL-12p70, IL-2 receptor alpha, cathepsin B, eotaxin, EGFR, FGF-basic, myeloperoxidase, RANTES, TGF-beta) were determined to be either statistically (p-value < 0.05) or marginally significantly (0.05 < p-value <0.1) changed in the selenium supplemented group as compared to placebo. Conclusion: Although independent validation of these results is needed, this study is the first of its kind to utilize high throughput fluorescence based protein multiplex panel in analyzing changes in the proteomic profile due to selenium supplementation. Results from this study provide insight into the ability of selenium to modulate numerous protein markers and thus impact various biological processes in humans.

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Interleukin-1α released from HSV-1-infected keratinocytes acts as a functional alarmin in the skin

Cited by 43 publications

References 48 publications

Interleukin 1α Is Critical for Resistance against Highly Virulent Aspergillus fumigatus Isolates

Interleukin 1α Is Critical for Resistance against Highly Virulent Aspergillus fumigatus Isolates

Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling

Effect of Selenium Supplementation on Proteomic Serum Biomarkers in Elderly Men

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