HR-1 Mice: A New Inflammatory Acne Mouse Model

Abstract

BackgroundThere is no appropriate in vivo animal model that reflects the inflammatory response of human acne.ObjectiveThis study investigated the effect of Propionibacterium acnes on the development of inflammatory acne-like lesions in four mouse strains with different degrees of immune response for the development of an optimal mouse model of inflammatory acne.MethodsHuman P. acnes suspensions (108 and 109 colony forming unit [CFU]/µl) were injected into the backs of HR-1, BALB/c, vitamin D receptor-knockout (VDR k/o), and severe combined immunodeficiency disease mice. Inflammation levels were evaluated two weeks after injection of P. acnes suspensions. In addition, histopathological examination and immunohistochemical staining of the expressions of inflammatory biomarkers (i.e., CD4+/CD8+ T lymphocytes, neutrophils, myeloperoxidase, interleukin-1β, matrix metalloprotease (MMP)-2, MMP-3, MMP-9, toll-like receptor (TLR)-2, LL-37, and integrin α6) were performed on tissue specimens.ResultsThe HR-1 mouse strain exhibited the most remarkable inflammatory reaction with epithelial proliferation and microcomedone-like cyst formation. HR-1 mice also demonstrated aberrant integrin expression in the epidermis around both inflamed lesions and newly formed microcomedones. These findings were more prominent in the group receiving 109 CFU/µl P. acnes than 108 CFU/µl. MMP-9 expression in HR-1 mice was also upregulated around the microcomedone-like cysts. Finally, expression levels of TLR-2 and LL-37 were higher in HR-1 and BALB/c mice than the VDR k/o and SCID mice strains.ConclusionP. acnes induces acneiform inflammation with small microcomedones in HR-1 mice. Therefore, the HR-1 mouse strain represents a good candidate for the development of a new inflammatory acne mouse model.

Propionibacterium acnes–induced immunopathology correlates with health and disease association

“…In initial experiments, we inoculated CD-1 mice in the back with 10 7 P. acnes based on a modified published protocol (13). As shown in Figure 1, intradermal inoculation of the mice with 10 7 acne-associated P. acnes RT5 strain HL043PA1 in PBS resulted in minimal lesions and was associated with rapid clearance of the bacteria from the site of inoculation, consistent with reports of difficulty inducing skin pathology with P. acnes in immunocompetent mice (13). Borrowing from other pathogen models of infection (15), we washed and inoculated P. acnes in media instead of PBS.…”

“…Bacterial infection is not needed for induction of acne in many models, which clearly limits the relevance of those models to the human condition. A frequently used platform induces skin inflammation on the back or ear of rodents using high intradermal inoculums of P. acnes (10 7 -10 9 live or dead P. acnes) (13,14).…”

Caenorhabditis elegansmounts a p38MAPKpathway‐mediated defence toCutibacterium acnesinfection

“…In 2013, a mouse model of chronic prostatic inflammation induced by C. acnes was developed using C57BL/6J mice, but it was preclinical and took 8 weeks for the entire observation (Shinohara et al, 2013). Jang et al (2015) utilised four types of mice to construct the mammalian acne model. They found clinical inflammation was more prominent in HR‐1 mice 2 weeks after the injection, which reflected the inflammatory responses of acne rather than the virulence of the anaerobe.…”

“…The study of C. acnes pathogenesis is particularly challenging, in part because there is no facile animal model to study host–pathogen interactions (Fischer et al, 2013; Shinohara et al, 2013). Although rabbits and HR‐1 mice can be inoculated with C. acnes via intradermal injection, these models usually require 2–4 weeks for the manifestation of comedones and inflammatory papules (Jang, Lee, Lee, Kim, & Lee, 2015; Wang et al, 2017). Similarly, the rat model of prostatic C. acnes infection is technically challenging and associated with significant cost (Olsson et al, 2012).…”

First Use of Optical Coherence Tomography on In Vivo Inflammatory Acne‐Like Lesions: A Murine Model

“…BIO‐17‐001‐Y1). Methods of inflammatory acne‐like induction were performed based on a modified approach previously introduced by Jang et al The skin was cleaned with ×1 phosphate‐buffered saline (PBS) followed by intradermal injection of live P. acnes bacteria in early log phase (10 µl of 1 × 10 8 CFU/µl) into the dorsal skin of SKH‐1 mice . The bacteria was cultured under anaerobic conditions at 37°C according to ATCC guidelines, with a target lesion yield of about 50–60%.…”