ZKKL Academic Sharing | Advances in Research on the Association Between Infection and Psoriasis

Article reprinted from: Chinese Journal of Dermatology and Venereology

Author: Shen Yangen, Yang Sen

[Abstract] Psoriasis is a common chronic inflammatory skin disease with unclear etiology and pathogenesis. In recent years, an increasing number of researchers have recognized that infectious factors play a significant role in the onset and progression of psoriasis. This review summarizes the roles of Streptococcus, Staphylococcus aureus, and Malassezia in the development and exacerbation of psoriasis.

[Keywords] Psoriasis; Streptococcus; Staphylococcus aureus; Malassezia

The clinical heterogeneity of psoriasis and its pronounced polygenic inheritance suggest that its onset and progression involve the combined effects of multiple factors, primarily genetic predisposition, infections, psychological stress, environmental influences such as certain medications, and immune‑mediated mechanisms. Infections have long been recognized as precipitating or exacerbating triggers in psoriasis. An increased secretion of IL‑17, leading to a Th17/Treg imbalance, is considered one of the key pathogenic mechanisms underlying autoimmune diseases. Some researchers propose that psoriasis is an autoimmune disorder characterized by a dysregulated Th1/Th2 balance; overexpression of pro‑inflammatory Th1 cytokines and underexpression of anti‑inflammatory Th2 cytokines in mucosal tissues and systemic compartments appear to contribute to the initiation, persistence, and recurrence of the disease, while disruption of the inflammatory mediator and cytokine network plays a critical role in the development of chronic plaque‑type psoriasis. In recent years, the role of microorganisms in the pathogenesis and progression of psoriasis has garnered growing attention; prevailing views hold that microbes may influence host immune responses and gene expression, thereby participating in the disease’s etiology and course. This review summarizes the roles of Streptococcus, Staphylococcus aureus, and Malassezia in the pathogenesis and progression of psoriasis from immunological and genetic perspectives.

1 Streptococcal Infection and Psoriasis

Streptococcus is a member of the Streptococcaceae family and is classified into three groups—group A (alpha‑hemolytic), group B (beta‑hemolytic), and group C (gamma‑hemolytic)—based on its hemolytic capacity. Streptococci exhibit strong invasive potential and produce a variety of virulence factors and exotoxins, including M protein, lipoteichoic acid, and hemolysins. As research into the etiology and pathogenesis of psoriasis has deepened, streptococcal infection—a key factor in the onset of acute guttate psoriasis—has gained widespread recognition. In recent years, domestic researchers have demonstrated that tonsillar streptococcal infection contributes to the development and progression of psoriasis; however, its underlying immunological mechanisms remain unclear. Some investigators have detected streptococcal M protein and keratin, among other superantigens, in peripheral blood cells and psoriatic lesions of patients, suggesting that these molecules can directly activate T cells and participate in the pathogenesis of psoriasis. Studies have reported that streptococcal (beta‑hemolytic) tonsillar colonization is significantly more prevalent in psoriasis patients than in healthy controls. In patients with concurrent streptococcal infection, abnormal activation of T lymphocytes has been observed, accompanied by elevated levels of cytokines such as CD4+, CD8+, IL‑17, and IL‑23. High expression of the IL‑23 receptor facilitates the egress of effector T cells from the tonsils, thereby triggering or exacerbating psoriasis. Human antimicrobial peptide LL‑37 has been shown to modulate innate immune responses in psoriasis, and streptococcal infection can activate CD14+CD16+ cells, further stimulating the immune system. IL‑37 promotes T cell proliferation and Th17 polarization. Research indicates that CD14 and CD16 expression correlate positively with disease severity, underscoring the critical role of IL‑37 in the pathogenesis of psoriasis. Peptidoglycan (PGN), a major component of the streptococcal cell wall, has recently been found in abundant quantities within psoriatic skin lesions. Studies suggest that Gram‑positive streptococci can engage toll‑like receptors (TLR2 and TLR4) to activate innate immune cells, contributing to the development and progression of arthropathic psoriasis. Foreign researchers using murine models of psoriatic skin lesions have identified ZC3H12A, an inducer of IL‑17A, which encodes the ribonuclease MCPIP1; MCPIP1 expression is markedly higher in lesional tissue compared to normal skin. Reports also indicate that in psoriatic epidermis infected with streptococci, the pathogenic HLA‑Cw6 allele is upregulated, along with activated cutaneous lymphoid T cells producing cytokines such as Th1, Th17, Th22, IL‑17A, IFN‑γ, and IL‑17F, as well as epidermal mediators like CXCL8, CXCL9, CXCL10, and CXCL11. These factors can activate Th17 cells, directly participating in the pathogenesis of psoriasis. CCL3, by modulating FOXP3 levels, may also influence the progression of psoriasis. FryL and colleagues have observed that Crohn’s disease patients are at greater risk of developing psoriasis, while psoriasis patients are more prone to Crohn’s disease; moreover, the intestinal microbiota of Crohn’s patients often harbors high abundances of Firmicutes and Streptococcus, which can stimulate innate immune responses and contribute to psoriasis pathogenesis. Some researchers have noted distinct bacterial profiles in both lesional and non‑lesional skin of psoriasis patients; biopsy specimens reveal that Firmicutes and Streptococcus are the most commonly encountered taxa. Genetic analyses further demonstrate that specific genetic loci associated with these bacteria are linked to innate immune regulation, suggesting shared susceptibility genes between psoriasis and Crohn’s disease. Additionally, foreign studies observing and analyzing psoriasis patients who underwent tonsillectomy have found that postoperative remission and improvement rates were significantly higher in those who had their tonsils removed compared to those who did not.

2 Staphylococcus aureus Infection and Psoriasis

Staphylococcus aureus is the most common pathogen responsible for suppurative infections in humans and is widely present on the human body surface as an opportunistic pathogen. The host defense mechanisms against S. aureus remain incompletely understood. Some studies have shown that patients with psoriasis harbor a greater abundance of S. aureus on their skin compared to healthy individuals, and they are more prone to its colonization. Prolonged, high‑level colonization of S. aureus on the skin can increase the likelihood of inflammatory changes and exacerbate psoriasis. Certain researchers have reported that the Th17 cell pathway exerts only limited control over S. aureus and provides relatively poor protection of the skin and mucosal barriers. Sedef GJ et al. used PCR to isolate large amounts of staphylococcal enterotoxins—pathogenic factors from S. aureus—from lesional skin in psoriasis patients, findings that were statistically significant when compared with healthy controls, suggesting that enterotoxins produced by S. aureus may be one of the key factors contributing to the aggravation of psoriasis. Myles IA et al. demonstrated that cytokines such as IL‑19, IL‑20, and IL‑24 can promote cutaneous infection with S. aureus in mice, while simultaneously downregulating the IL‑1β and IL‑17A pathways. Human keratinocytes produce antimicrobial peptides and proteins (AMPs) that help protect the skin from infection. Recent research has revealed that the cytokine combination of IL‑17A/TNF‑α serves as a potent inducer of AMP production. Overseas investigators have found that cIAP‑2 can inhibit the anti‑apoptotic effects of S. aureus peptidoglycan on keratinocytes, thereby promoting the proliferation and differentiation of keratinocytes in psoriasis. In terms of genetics, studies using mouse models of psoriasis have identified the SLURP‑1 gene as a regulator of the expression of inflammatory cytokines—including IL‑17 and IL‑22—as well as TNF‑α. SLURP‑1 may function as an important factor governing keratinocyte proliferation and differentiation, and it can significantly suppress the growth of S. aureus.

3 Malassezia Infection and Psoriasis

Malassezia is a lipophilic fungus; most strains possess lipase and are embedded within the glucan-rich cell wall and/or cellular membrane system. Lipase hydrolyzes lipids into fatty acids, providing essential nutrients for its own metabolism. It primarily colonizes areas of the human body rich in sebaceous glands, such as the chest, back, scalp, face, and neck, and is considered an opportunistic pathogen. The lipophilic and hydrophilic components of Malassezia can trigger host cells to release IL‑8, activate the complement system, and induce the migration of immune cells into the dermis. Hydrophobic constituents may also promote the development and exacerbation of psoriasis by modulating Th1/Th2 responses in peripheral blood. On normal skin, Malassezia can elicit the production of transforming growth factor‑β1 and interleukin‑10, while suppressing pro‑inflammatory cytokines such as IL‑1, IL‑6, and TNF‑α, thereby dampening host immunity and enabling long-term commensalism. In skin with compromised barrier integrity, Malassezia can amplify inflammatory responses and drive excessive epidermal hyperproliferation. HBDs can confer resistance to microbial infection by upregulating HBD‑2 expression, and cytokines including IL‑1, IL‑2, IL‑6, IL‑8, and IL‑12 can induce this enhanced HBD‑2 expression. Foreign researchers conducted genetic polymorphism analyses of the HBD region on chromosome 8 in psoriasis patients and healthy controls, revealing significantly higher HBD‑2 expression in psoriasis patients compared with the control group. James A.G. et al. found that HBD‑2 and TNF‑α were markedly overexpressed in psoriatic lesions relative to normal skin, with expression levels increasing alongside disease severity and showing a significant positive correlation with the Psoriasis Area and Severity Index (PASI). These findings suggest that Malassezia plays a crucial role in the onset and progression of psoriasis. In some patients, early clinical manifestations of psoriasis may include increased dandruff; spherical Malassezia and restricted Malassezia are major contributors to this symptom. Some investigators propose that these two species dominate psoriatic lesions. Furthermore, Malassezia can stimulate keratinocyte proliferation via Toll‑like receptor or NOD‑like receptor signaling pathways, which correlates with the pathogenesis of psoriasis. Early treatment with antifungal agents in patients with psoriatic plaques limited to the scalp and concurrent Malassezia infection can inhibit lesion progression; however, the underlying mechanisms remain unclear and require further investigation. Mattozzi C. et al. have suggested that ketoconazole helps improve outcomes in psoriasis patients co‑infected with Malassezia, a view that has gained broad acceptance among European scholars.

4 Conclusion

In summary, studies in immunology and genetics have demonstrated that Streptococcus, Staphylococcus aureus, and Malassezia are involved in the onset and progression of psoriasis. Anti‑infective therapies can shorten the disease course and improve patients’ quality of life, providing valuable guidance for psoriasis management. At present, both domestically and internationally, research on other microorganisms—such as viruses, Mycobacterium tuberculosis, and non‑tuberculous mycobacteria—has begun, though reports remain limited. Researchers may further investigate the mechanisms underlying the occurrence and development of infections complicating psoriasis, as well as the immune pathways through which microbial infections trigger or exacerbate the disease.

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