Heat Shock Proteins as Immunomodulants

Zininga, Tawanda; Ramatsui, Lebogang; Shonhai, Addmore

doi:10.3390/molecules23112846

Cited by 269 publications

(207 citation statements)

References 119 publications

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“…Housekeeping-like proteins identified here mostly function intracellularly, and they serve as alarm signals to alert the host defense system to injury when secreted outside of the cell (145). There is evidence that in the extracellular space, some of the housekeeping proteins such as heat shock proteins, have anti-inflammatory functions (146), while histone proteins have antimicrobial activity (147). Given high sequence similarity to host housekeeping proteins, could it be that some of the tick housekeeping-like proteins play roles in promoting tick feeding through anti-inflammatory and anti-microbial activity?…”

Section: Resultsmentioning

confidence: 99%

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Kim

Tirloni

Pinto

et al. 2019

Preprint

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24Amblyomma americanum ticks transmit more than a third of human tick-borne disease 25 (TBD) agents in the United States. Tick saliva proteins are critical to success of ticks as vectors 26 of TBD agents, and thus might serve as targets in tick antigen-based vaccines to prevent TBD 27 infections. We describe a systems biology approach to identify, by LC-MS/MS, saliva proteins 28 (tick=1182, rabbit=335) that A. americanum ticks likely inject into the host every 24 h during the 29 first 8 days of feeding, and towards the end of feeding using two different sample preparation 30 approaches (in-gel and in-solution). The in-gel approach determined molecular identification of 31 predominant protein bands in tick saliva, and the in-solution added depth to discovery of 32 proteins. Searching against entries in GenBank grouped tick and rabbit proteins in this study into 33 27 and 25 functional categories. Aside from housekeeping-like proteins, majority of tick saliva 34 proteins belong to the tick-specific (no homology to non-tick organisms: 32%), protease 35 inhibitors (13%), proteases (8%), glycine-rich proteins (6%) and lipocalins (4%) categories.36 Global secretion dynamics analysis suggests that majority (74%) of proteins in this study are 37 associated with regulating initial tick feeding functions and transmission of pathogens as they are 38 secreted within 24-48 h of tick attachment. Comparative analysis of the A. americanum tick 39 saliva proteome to five other tick saliva proteomes identified 284 conserved tick saliva proteins:40 we speculate that these regulate critical tick feeding functions and might serve as tick vaccine 41 antigens. We discuss our findings in the context of understanding A. americanum tick feeding 42 physiology as a means through which we can find effective targets for a vaccine against tick 43 feeding. 44 45 3 46 Author Summary 47The lone star tick, Amblyomma americanum, is a medically important species in US that 48 transmits 5 of the 16 reported tick-borne disease agents. Most recently, bites of this tick were 49 associated with red meat allergies in humans. Vaccination of animals against tick feeding has 50 been shown to be a sustainable and effective alternative to current acaricide based tick control 51 method which has several limitations. The pre-requisite to tick vaccine development is to 52 understand the molecular basis of tick feeding physiology. Toward this goal, this study has 53 identified proteins that A. americanum ticks inject into the host at different phases of its feeding 54 cycle. This data set has identified proteins that A. americanum inject into the host within 24-48 h 55 of feeding before it starts to transmit pathogens. Of high importance, we identified 284 proteins 56 that are present in saliva of other tick species, which we suspect regulate important role(s) in tick 57 feeding success and might represent rich source target antigens for a tick vaccine. Overall, this 58 study provides a foundation to understand the molecular mechanisms regulating tick feeding 59 p...

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Section: Resultsmentioning

confidence: 99%

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Kim

Tirloni

Pinto

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…Other than suppressing the expression and activation of oncogenic proteins, HSP90 inhibition has recently been found to positively modulate the effect of cancer immunotherapy [148]. HSP90 inhibition using Ganetespib has been shown to increase the expression of interferon response genes, such as IFIT1, IFIT2, and IFIT3, which promote killing of melanoma cells by T cells.…”

Section: Hsp27 Hsp90 Myelomamentioning

confidence: 99%

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Yun

Kim

Lim

et al. 2019

Cells

201

158

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Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their molecular weights, and they include HSP27, HSP40, HSP60, HSP70, and HSP90. HSPs function in diverse physiological and protective processes to assist in maintaining cellular homeostasis. In particular, HSPs participate in protein folding and maturation processes under diverse stressors such as heat shock, hypoxia, and degradation. Notably, HSPs also play essential roles across cancers as they are implicated in a variety of cancer-related activities such as cell proliferation, metastasis, and anti-cancer drug resistance. In this review, we comprehensively discuss the functions of HSPs in association with cancer initiation, progression, and metastasis and anti-cancer therapy resistance. Moreover, the potential utilization of HSPs to enhance the effects of chemo-, radio-, and immunotherapy is explored. Taken together, HSPs have multiple clinical usages as biomarkers for cancer diagnosis and prognosis as well as the potential therapeutic targets for anti-cancer treatment.

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“…A number of Hsp (Hsp 90, Hsp 70, Hsp 60, Hsp 40 and Hsp 27) are involved in different features of the immune response, for instance modulating the patterns of several cytokines [80]. As different patterns of Hsp may be induced by heat and oxidative stress, a still unclear but potentially relevant link between temperature and ROS-producing stimuli on one side and immune response on the other side could exist.…”

Section: Immune Effectsmentioning

confidence: 99%

Balance between Health Risks and Benefits for Outdoor Workers Exposed to Solar Radiation: An Overview on the Role of Near Infrared Radiation Alone and in Combination with Other Solar Spectral Bands

Grandi

D’Ovidio

2020

IJERPH

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Near infrared or infrared A (IRA) accounts for over 40% of the solar spectrum (SS) and is able to reach subcutaneous tissue as well as the retina. Outdoor workers are occupationally exposed to solar radiation (SR), but the level of exposure may differ widely depending on the job performed, time spent outdoors, latitude, altitude, season, personal protection, etc. Until now, risk assessment and management for outdoor workers has focused on the prevention of both acute and long-term effects on the eye and the skin due to solar ultraviolet radiation (UVR) with little consideration of the other components of the SS (a possible exception is represented by visible radiation with reference to the eye). A growing body of evidence coming from in vitro studies indicates that IRA is involved in cellular reactive oxygen species (ROS) production and may interfere with the respiratory chain in the mitochondria. Moreover, it can modulate gene expression and some metabolic pathways. The biological action of IRA is only partly attributable to a thermal mechanism, should it be also involved in photochemical ones. The cellular and molecular pathways affected by IRA are partly similar and partly different with respect to those involved in the case of visible ultraviolet A (UVA) and ultraviolet B (UVB) radiation. Consequently, the net effect of the SS is very difficult to predict at different levels of the biological organization, making more difficult the final balance of health risk and benefits (for the skin, eye, immune system, blood pressure, etc.) in a given exposure situation. Moreover, few in vivo studies and no epidemiological data are presently available in this regard. Investigating this topic may contribute to better defining the individual exposome. More practically, it is expected to bring benefits to the risk assessment and management for outdoor workers exposed to SS, contributing to: (1) better definition of the individual profiles of susceptibility, (2) more focused preventive and protective measures, (3) better implementation of the health surveillance and (4) a more effective information and training.

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Heat Shock Proteins as Immunomodulants

Cited by 269 publications

References 119 publications

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Balance between Health Risks and Benefits for Outdoor Workers Exposed to Solar Radiation: An Overview on the Role of Near Infrared Radiation Alone and in Combination with Other Solar Spectral Bands

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