Streptococcus pyogenes –induced cutaneous lymphocyte antigen–positive T cell–dependent epidermal cell activation triggers T H 17 responses in patients with guttate psoriasis

Ruiz-Romeu, Ester; Ferrán, Marta; Sagristà, Marc; Gómez, Julia María Martínez; Giménez-Arnau, A.M.; Herszényi, Krisztina; Holló, Péter; Celada, Antonio; Pujol, Ramón M.; Santamaria‐Babí, Luis F.

doi:10.1016/j.jaci.2016.02.008

Cited by 43 publications

(44 citation statements)

References 51 publications

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“…Evidence implicates that GAS-specific Th17 cells are involved in GAS related autoimmune disorders [24]. It is reported that intranasal GAS infection promotes infiltration of GAS-specific Th17 cells into the brain and causes immunopathology in the brain [25].…”

Section: Resultsmentioning

confidence: 99%

Co-Activation of Th17 and Antibody Responses Provides Efficient Protection against Mucosal Infection by Group A Streptococcus

Chen

et al. 2016

PLoS ONE

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Conserved protein antigens among serotypes of group A Streptococcus pyogenes (GAS) have been focused for vaccine development because of the diversity of GAS serotypes and risks of autoimmunity post-GAS infection. Precise delineation of protective immune response to each of GAS antigens is critical for vaccine efficacy and safety. We recently reported that immunization with SrtA of GAS provides Th17-dependent clearance of heterologous serotypes of GAS in NALT. SCPA is a surface virulence molecule of GAS and known to induce antibody-mediated protection against GAS. We hypothesized that co-immunization with SrtA and SCPA would provide more efficient protection by eliciting combined Th17 and antibody responses. The present study showed that mice that were intranasally co-immunized with SrtA/SCPA cleared GAS more efficiently than the mice that were immunized with either SrtA or SCPA individually, and as efficient as the mice that experienced repeated GAS infections. The co-immunization induced Th17 and robust SCPA antibody responses, accompanied by a rapid influx of neutrophils and high myeloperoxidase activity in NALT, suggesting that simultaneous induction of mucosal Th17 and neutralizing antibody responses offers more effective GAS elimination through rapid infiltration and activation of neutrophils. Moreover, Th17 response was strongly induced in mice that experienced repeated GAS-infection and maintained at a high level even after the bacteria were cleared; whereas, it was moderately induced and promptly returned to baseline following bacterial elimination in SrtA/SCPA co-immunized mice. Additional results showed that the survival rate of systemic challenge was significantly higher in infection experienced than in co-immunized mice, indicating that more immune elements are required for protection against systemic than mucosal GAS infection.

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Section: Resultsmentioning

confidence: 99%

Co-Activation of Th17 and Antibody Responses Provides Efficient Protection against Mucosal Infection by Group A Streptococcus

Chen

et al. 2016

PLoS ONE

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“…In contrast, microbial antigens derived from candida or staphylococci preferentially induce Th17 cells . Guttate psoriasis is induced by molecular mimicry after infection with streptococci . Lichen planus is associated with HCV infection …”

Section: Trigger Factors and Early Eventsmentioning

confidence: 99%

“…49 Guttate psoriasis is induced by molecular mimicry after infection with streptococci. 50 Lichen planus is associated with HCV infection. 51 Lessons learned for specific therapy…”

Section: Trigger Factors and Early Eventsmentioning

confidence: 99%

Immune response patterns in non‐communicable inflammatory skin diseases

Eyerich

2018

Acad Dermatol Venereol

125

143

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Non‐communicable inflammatory skin diseases (ncISD) such as psoriasis or atopic eczema are a major cause of global disease burden. Due to their impact and complexity, ncISD represent a major challenge of modern medicine. Dermatology textbooks describe more than 100 different ncISD based on clinical phenotype and histological architecture. In the last decades, this historical description was complemented by increasing molecular knowledge – and this knowledge is now being translated into specific therapeutics. Combining the enormous advances made in lymphocyte immunology and molecular genetics with clinical and histological phenotyping reveals six immune response patterns of the skin – type I immune cells cause the lichenoid pattern characterized by immune‐mediated cell death of keratinocytes; type II immune cells underlie the eczematous pattern with impaired epidermal barrier, infection and eosinophils as well as the bullous pattern with loss of epithelial integrity; Th17 cells and ILC3 mediate the psoriatic pattern characterized by acanthosis, high metabolic activity and neutrophils; dysbalance of regulatory T cells causes either the fibrogenic pattern with rarefication of cells and dermal thickening or the granulomatous pattern defined by formation of granulomas. With more and more specific therapeutic agents approved, classifying ncISD also according to their immune response pattern will become highly relevant. This review defines the six immune response patterns of ncISD and highlights therapeutic strategies targeting key lymphocyte mediators.

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“…Superantigens from GAS have been demonstrated to enhance T cell expression of CLA + , which is a carbohydrate‐moiety expressed by 80% of T cells in the skin, and the abundance of CLA + CD8 + T cells in the blood of patients with psoriasis correlates with disease severity . CLA + T cells in the tonsils and GP lesions of the same patient show identical TCRβ rearrangement (Vβ2 + ), suggesting that migration of these cells occurs from the tonsils to the skin . Once in the skin, the CLA + T cells interact with lesional epidermal cells and induce a dominant Th17 response .…”

Section: Complications Arising From Gas Pharyngitismentioning

confidence: 99%

“…183 CLA + T cells in the tonsils and GP lesions of the same patient show identical TCR rearrangement (V 2 + ), suggesting that migration of these cells occurs from the tonsils to the skin. 184 Once in the skin, the CLA + T cells interact with lesional epidermal cells and induce a dominant Th17 response. 185 Some studies have reported that tonsillectomy results in improvement of psoriasis in the majority of cases and is associated with a reduction in the frequency of skin-homing T cells in the blood that were reactive to peptides derived from human epidermal keratins and streptococcal M proteins.…”

Section: Gpmentioning

confidence: 99%

Group A streptococcal pharyngitis: Immune responses involved in bacterial clearance and GAS-associated immunopathologies

Soderholm

Barnett

Sweet

et al. 2017

Journal of Leukocyte Biology

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Streptococcus pyogenes, the Group A Streptococcus (GAS), is the most common cause of bacterial pharyngitis in children and adults. Innate and adaptive host immune responses are fundamental for defense against streptococcal pharyngitis and are central to the clinical manifestation of disease. Host immune responses also contribute to the severe poststreptococcal immune diseases that constitute the major disease burden for this organism. However, until recently, little was known about the host responses elicited during infection. Cellular mediators of innate immunity used during host defense against GAS include epithelial cells, neutrophils, macrophages, and dendritic cells (DCs), which are reported to secrete a number of soluble inflammatory mediators, such as antimicrobial peptides (AMPs); eicosanoids, including PGE and leukotriene B4 (LTB ); chemokines; and proinflammatory cytokines. Th1 and Th17 responses play significant roles in adaptive immunity in both murine models of GAS pharyngitis and in human tonsil tissue. A number of inflammatory complications are associated with GAS pharyngitis, which can lead to chronic disease in patients. These include scarlet fever, tonsillar hypertrophy, and sleep apnea, as well as postinfectious sequelae, such as acute rheumatic fever (ARF), poststreptococcal glomerulonephritis, and guttate psoriasis (GP). This review aims to present the current state of knowledge on innate and adaptive immune responses elicited during GAS pharyngitis, mechanisms by which GAS evades these responses, the emerging role of the pharyngeal microbiota, and how the interplay among these factors can influence the outcome of infection and inflammation-related complications.

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Streptococcus pyogenes –induced cutaneous lymphocyte antigen–positive T cell–dependent epidermal cell activation triggers T H 17 responses in patients with guttate psoriasis

Abstract: This study reveals a dominant TH17 response of cutaneous lymphocyte antigen-positive T cells activated by epidermal cells and S pyogenes in patients with GP.

Cited by 43 publications

References 51 publications

Co-Activation of Th17 and Antibody Responses Provides Efficient Protection against Mucosal Infection by Group A Streptococcus

Co-Activation of Th17 and Antibody Responses Provides Efficient Protection against Mucosal Infection by Group A Streptococcus

Immune response patterns in non‐communicable inflammatory skin diseases

Group A streptococcal pharyngitis: Immune responses involved in bacterial clearance and GAS-associated immunopathologies

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