Imiquimod does not elicit inflammatory responses in the skin of the naked mole rat (Heterocephalus glaber)

Abstract

Objective: Naked mole rat (Heterocephalus glaber) has recently attracted interest in biomedical research due to its exceptional longevity, cancer resistance and tolerance to potentially harmful conditions or stimuli. Given its unique attributes, this study was designed to characterize inflammatory skin reactions of this animal to topical application of imiquimod, a toll-like receptor 7 and 8 agonist that triggers psoriasis-like skin reaction. Results: Imiquimod did not cause the expected psoriasis-like skin changes. There was no epidermal thickening and a straight epidermo-dermal boundary was maintained. There was no parakeratosis and the granular layer of epidermis was well formed. In the dermis, there was no leukocyte infiltration. This points to an exceptional nature of inflammatory/immune responses of this animal, but the mechanism could not be explained by our results. Naked mole rat could be a valuable negative model for studying psoriasis and other inflammatory skin conditions but as a prerequisite, there is need for further investigations to establish the mechanisms behind its lack of response to imiquimod.

Macrophages from naked mole-rat possess distinct immunometabolic signatures upon polarization

“…However, hematopoietic stem cells of aged NMR demonstrate no age-related upregulation of inflammatory markers, remain quiescent and possess an increased cell cycle length ( 2 ), showing lack of “inflammaging” hallmarks ( 7 ), which is consistent with the concept of juvenile physiology proposed for NMR ( 8 ). In line with this, some in vivo studies reported that NMR is resistant to inflammation-associated diseases, such as chemically induced psoriasis ( 9 , 10 ). Also, the efficiency of the innate arm of the immune system is in agreement with the ability to control gut microflora ( 11 ) by the production of highly active antimicrobial peptides ( 12 ).…”

Imiquimod-induced pruritus in female wild-type and knockin Wistar rats: underscoring behavioral scratching in a rat model for antipruritic treatments

“…Considerations to further isolate its effects in our model can improve pathway understanding in this model. [23][24][25][26][27] Finally, additional investigations substantiating scratching in other in vivo models of itch further highlight its behavioural importance endpoint to the evaluation in skin disease [14].…”

Bodyweight, locomotion, and behavioral responses of the naked mole rat (Heterocephalus glaber) to lipopolysaccharide administration

“…In NMR, the immune system exhibits some peculiarities in terms of cellular composition with a predominance of myeloid lineage cells and a lack of natural killer cells (Cheng et al 2017;Hilton et al 2019). It is therefore likely that the immune system of the NMR is a key contributor to its prolonged health span and cancer resistance and the same has been speculated in recent reports (Zhao et al 2014;Hilton et al 2019;Kisipan et al 2020;Taguchi et al 2020). The establishment of this animal as a model for aging, cancer, and inflammatory diseases, therefore, requires characterization of the immunity and its interactions with the other body systems and biological processes in the animal.…”

“…These include cancer resistance, tolerance to hypoxia, pain, and itch; and an extended lifespan and health span compared to other rodents despite high oxidative damage (Andziak et al 2006 ; Buffenstein 2008 ; Larson and Park 2009 ; Liang et al 2010 ; Smith et al 2010 ; Tian et al 2015 ; Omerbašić et al 2016 ; Tan et al 2017 ; Kurz et al 2017 ; Ruby et al 2018 ). The animal has also been shown to exhibit resistance to age-related and inflammatory conditions (Hilton et al 2019 ; Kisipan et al 2020 ; Taguchi et al 2020 ). Due to its unique biological attributes, the animal has been found of great interest in biomedical research.…”