Malassezia Globosa Aggravates Atopic Dermatitis by Influencing the Th1/Th2 Related Cytokines in Mouse Models

Abstract

Purpose: To establish atopic dermatitis (AD) mouse models infected with Malassezia globosa and study its effects and potential mechanisms.

Methods: Twenty - four male BALB/c mice were randomly allocated into four groups: control, AD, M (normal mice treated with olive oil fungus suspension), and AD + M (AD mice treated with the same suspension). DNFB was used to induce the AD model. The M and AD + M groups were treated with Malassezia suspension. Body weight, scratching behavior, and skin lesion scores of mice were recorded. Skin tissues underwent HE and PAS staining, viable fungal flora counting, and Th1/Th2 cytokine detection via flow cytometry.

Results: The AD mouse models infected with Malassezia globosa were successfully set up. The AD + M group scratched more often. On days 8, 12, and 16, the AD group's skin lesion scores were (9.00±0.89), (10.17±0.87), (9.17±0.75), while those of the AD + M group were (11.00±0.82), (10.83±0.75), (10.83±0.75) (P<0.05). The AD + M group had more Malassezia colonization (P<0.001). The M group displayed a Th1 response. The AD + M group enhanced Th1 response and increased Th2 cytokines like IL - 4 and IL - 10 (P<0.05). The control group had normal skin with minimal scratching and low fungal counts.

Conclusion: Malassezia causes inflammation in normal and AD - like skin, with worse inflammation when the skin barrier is damaged. Targeting Malassezia might alleviate AD inflammation, offering new AD treatment directions.

Keywords: atopic dermatitis; fungal colonization; immune response; inflammatory cytokines; mouse model.

Figure 1

Construction of AD mouse model treated with Malassezia globosa.

Figure 2

Effects of Malassezia on DNFB-induced AD-like Mice. (A) General appearance of dorsal skin lesions in mice of different treatment groups on days 4, 8, 12, and 16. (B) Dermatitis scores of mice in different treatment groups. (C) Scratching frequencies of mice in different treatment groups. (D) Changes in body weights of mice in different treatment groups. ns P > 0.05, *** P < 0.001.

Figure 3

Results of Histopathological Manifestations and live Malassezia population counts. (A) Histopathological manifestations of dorsal skin lesions of mice in different treatment groups (HE × 200). (B) Colonization of Malassezia globosa in dorsal skin lesions of mice in M Group and AD+M Group. Malassezia spores were indicated by red arrows (PAS × 200). (C) Results of live Malassezia population counts in skin lesion tissues of mice in M Group and AD+M Group. Each data point represents one mouse, with n = 6 mice in each group. The results were expressed as mean ± standard deviation. The t-test was used to determine statistical significance. *** P < 0.001.

Figure 4

Malassezia Colonization Aggravated Th1/Th2-Related Inflammatory Responses in Normal and AD-like Mice. (A) Scatter plot of cytokine distribution. (B) Secretion of cytokines (IL-1β, IL-4, IL-6, IL-10, IFN-γ, TNF-α, IL-2, IL-12) in dorsal skin lesions of mice in different treatment groups. (C) Comparison of cytokines (IL-1β, IL-4, IL-10, IFN-γ, TNF-α) in dorsal skin lesions of mice in different treatment groups. The values were shown as the mean ± standard deviation of 6 mice. Unpaired t-tests were used among four groups. ns P > 0.05, *P < 0.05, *** P < 0.001.