Ann Dermatol.  2019 Feb;31(1):22-28. 10.5021/ad.2019.31.1.22.

Efficacy of Bacteriophages in Propionibacterium acnes-Induced Inflammation in Mice

• Kim MJ
• Eun DH
• Kim SM
• Kim J
• Lee WJ

• KMID: 2430797
• DOI: http://doi.org/10.5021/ad.2019.31.1.22

Abstract

BACKGROUND
Bacteriophages have been introduced as living drugs for infectious diseases; thus, they may provide an alternative to conventional acne therapeutics in patients with non-responsive acne.
OBJECTIVE
We investigated the effect of bacteriophages using an acne mouse model with Propionibacterium acnes-induced inflammatory nodules by clinical examination, pathology, and immunohistochemical analysis.
METHODS
A human-isolated P. acnes suspension (10⁹ colony forming units/µl) was injected into the backs of HR-1 mice. Group A was used as a control, Group B was injected on the back with P. acnes 4 weeks following the initial P. acnes suspension injection, and group C was injected on the back with P. acnes and bacteriophages 4 weeks following the initial P. acnes suspension injection. Clinical and histopathological evaluations were performed.
RESULTS
Inflammatory nodule size decreased with time in all groups. Group C showed the greatest decrease in size, followed by group B and group A. The histopathological findings showed a decrease in epidermal thickness and the number and size of microcomedone-like cysts in groups B and C compared to group A. Immunohistochemistry revealed similar expression of integrin α6, the epidermal proliferation marker, infiltration of CD4/CD8 T cells and neutrophils, and expression of myeloperoxidase, interleukin-1β, toll-like receptor-2, LL-37, and matrix metalloproteinase-2/3/9 in all three groups.
CONCLUSION
Using an acne mouse model with P. acnes-induced inflammatory nodules, we demonstrate that bacteriophages may constitute an alternative to conventional acne therapies. However, additional studies are needed for human applications.

Keyword

Acne vulgaris; Bacteriophage; Mice; Propionibacterium acnes

MeSH Terms

Acne Vulgaris
Animals
Bacteriophages*
Communicable Diseases
Humans
Immunohistochemistry
Inflammation*
Mice*
Neutrophils
Pathology
Peroxidase
Propionibacterium acnes
Propionibacterium*
T-Lymphocytes
Peroxidase

Figure

• 

  Fig. 1 (A) Changes in inflammatory nodule size in groups A, B, and C. The size of the inflammatory nodules in all groups decreased with time. (B) Changes in inflammatory nodule size in groups A, B, and C. The size of the inflammatory nodules in all groups decreased with time. The changes in size between groups B/C and group A were significantly different at weeks 1, 2, 3, and 4. The changes in size between group B and group C were significantly different at week 2 and 4.

• 

  Fig. 2 (A) Histopathological findings of group A, group B and group C at week 4 (H&E, ×200). (B) Changes in epidermal thickness. The epidermal thickness of the inflammatory nodules decreased with time, especially in group C, followed by group B and group A. However, there were no statistically significant differences. (C) Changes in the number of microcomedone-like cysts. The number of microcomedone-like cysts decreased with time, especially in group C, followed by group B and group A. However, there were no statistically significant differences. (D) Changes in the size of microcomedone-like cysts. The size of the microcomedone-like cysts decreased with time, especially in group C, followed by group B and group A. However, there were no statistically significant differences.

• 

  Fig. 3 (A) Immunohistochemistry analysis. Inflammatory biomarker expression was similar in all groups. There were no statistically significant differences except for integrin α6 between group B and group C. (B) Immunohistochemistry with integrin α6 in group A, group B and group C at week 2 (×200). IL: interleukin, MMP: matrix metalloproteinase, MPO: myeloperoxidase, TLR: toll-like receptor.

• 

  Fig. 4 Western blot analysis showed immunoreactivity to the immunoglobulin G antibody against Propionibacterium acnes (P. acnes) following treatment with P. acnes.

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