Imbalance of immune responses in patients with chronic and widespread fungal skin infection

Leibovici, Vera; Evron, Ruth; Axelrod, Ofra; Westerman, Maxwell P.; Shalit, Meir; Barak, V.; Frankenburg, Shoshana

doi:10.1111/j.1365-2230.1995.tb01355.x

Cited by 30 publications

(23 citation statements)

References 9 publications

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“…Nucleotide and deduced amino acid sequences of recombinant Tri r 4. The NH 2 -terminal amino acid residues (positions [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] contain the conserved features of a signal peptide with a predicted cleavage site between Ala 19 and Phe 20 . Underlined regions represent amino acid sequences previously obtained for the NH 2 terminus and for six enzymatically generated peptides of natural Tri t 4.…”

Section: Methodsmentioning

confidence: 99%

Trichophyton Antigens Associated with IgE Antibodies and Delayed Type Hypersensitivity

Woodfolk¹,

Wheatley²,

Piyasena³

et al. 1998

Journal of Biological Chemistry

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The dermatophyte fungus Trichophyton exhibits unique immunologic properties by its ability to cause both immediate and delayed type hypersensitivity. An 83-kDa Trichophyton tonsurans allergen (Tri t 4) was previously shown to elicit distinct T lymphocyte cytokine profiles in vitro. The homologous protein, Tri r 4, was cloned from a Trichophyton rubrum cDNA library, and the recombinant protein was expressed in Pichia pastoris. This 726-amino acid protein contained an arrangement of catalytic triad residues characteristic of the prolyl oligopeptidase family of serine proteinases (Ser-Asp-His). In addition, a novel Trichophyton allergen, encoding 412 amino acids, was identified by its human IgE antibody-binding activity. Sequence similarity searches showed that this allergen, designated Tri r 2, contained all of the conserved residues characteristic of the class D subtilase subfamily (41-58% overall sequence identity). Forty-two percent of subjects with immediate hypersensitivity skin test reactions to a Trichophyton extract exhibited IgE antibody binding to a recombinant glutathione S-transferase fusion protein containing the carboxyl-terminal 289 amino acids of Tri r 2. Furthermore, this antigen was capable of inducing delayed type hypersensitivity skin test reactions. Our results define two distinct antigens derived from the dermatophyte Trichophyton that serve as targets for diverse immune responses in humans.Dermatophyte fungi of the genus Trichophyton colonize keratinized tissues in humans including nails, hair shafts, and the stratum corneum of the skin. Trichophyton tonsurans, Trichophyton mentagrophytes, and Trichophyton rubrum are common causes worldwide of tinea capitis, athlete's foot, and onychomycosis (infection of the nail beds) (1). An estimated 30 -70% of adults are asymptomatic carriers of these pathogens, and the incidence of symptomatic disease increases with age (2). The immune response to antigens derived from Trichophyton is unique in that both immediate hypersensitivity (IH) 1 and delayed type hypersensitivity (DTH) skin test reactions are induced. Studies suggest that the nature of the underlying immune response to Trichophyton antigens is related to the severity of dermatophytosis; IH skin tests are associated with chronic recurrent infections characterized by low-grade inflammatory lesions and the presence of IgE antibodies (Ab) (4 -7). In contrast, DTH reactions are associated with highly inflamed lesions that resolve spontaneously and a resistance to re-infection (4, 8 -13). The implication of these findings is that cellmediated immune responses to Trichophyton are more effective at eradicating infection and may confer protection. Chronic dermatophytosis has been associated with allergic disease in the respiratory tract in individuals with immediate hypersensitivity (14 -17). Furthermore, exposure to Trichophyton proteins may result in bronchial sensitization and symptomatic asthma that can be controlled with systemic antifungal therapy (7,18,19).Experimental mouse models support a role...

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Section: Methodsmentioning

confidence: 99%

Trichophyton Antigens Associated with IgE Antibodies and Delayed Type Hypersensitivity

Woodfolk¹,

Wheatley²,

Piyasena³

et al. 1998

Journal of Biological Chemistry

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“…In keeping with this, it has been proposed that protracted antigen exposure can induce immunologic unresponsiveness, or anergy, by activating suppressor T cells which then downregulate cell-mediated responses (20). However, several studies have failed to demonstrate diminished T-cell proliferative responses to dermatophyte antigens in patients with IH (51,66,74,124). Alternatively, properties of the fungus itself may prevent the development of cell-mediated responses.…”

Section: Immediate Hypersensitivity: a Marker Of Immune Status?mentioning

confidence: 99%

Allergy and Dermatophytes

Woodfolk

2005

Clin Microbiol Rev

143

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Tinea pedis (athlete's foot) and onychomycosis (infection of the toenails) caused by the dermatophyte fungus Trichophyton are highly prevalent in adults. Several Trichophyton allergens have been identified based on elicitation of immunoglobulin E antibody-mediated immediate-hypersensitivity (IH) responses. Evidence of an etiologic role for Trichophyton in asthma in some subjects with IH and chronic dermatophytosis is provided by bronchial reactivity to Trichophyton. Improvement of asthma after systemic antifungal treatment corroborates this link. A unique feature of Trichophyton allergens is the ability of the same antigen to elicit delayed-type hypersensitivity (DTH) in individuals who lack IH reactivity. Delayed responses appear to confer protection, while IH responses do not, based on the association with acute versus chronic skin infection. The amino acid sequence identity of Trichophyton allergens with diverse enzyme families supports a dual role for these proteins in fungal pathogenesis and allergic disease. Characterizing the immunologic properties of Trichophyton allergens and defining immune mechanisms which drive dichotomous responses are pivotal to understanding the dermatophyte-allergy relationship. Recent studies have identified DTH-associated major T-cell epitopes which could facilitate the development of peptide vaccines. Characterization of additional molecular targets by using new techniques may aid not only in the eradication of infection but also in the resolution of allergic symptoms

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“…[21][22][23] This small series illustrates the potential utility of imiquimod in the treatment of earlobe keloids and provides further support for the proposed mechanism of action of imiquimod. 24,25 Because keloids located at other anatomic locations may respond differently, similar studies are needed before any conclusions regarding the activity of adjuvant imiquimod therapy in keloids located on areas other than the earlobe can be made. In addition, although the historically high recurrence rate of keloids with surgical excision does not suggest surgical excision with small margins alone would have an improved recurrence rate, it is possible that the excision technique with margins used in the current study may have contributed to the improved recurrence rate.…”

Section: Discussionmentioning

confidence: 98%

Successful Treatment of Earlobe Keloids with Imiquimod after Tangential Shave Excision

Stashower¹

2006

Dermatologic Surgery

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Imbalance of immune responses in patients with chronic and widespread fungal skin infection

Cited by 30 publications

References 9 publications

Trichophyton Antigens Associated with IgE Antibodies and Delayed Type Hypersensitivity

Trichophyton Antigens Associated with IgE Antibodies and Delayed Type Hypersensitivity

Allergy and Dermatophytes

Successful Treatment of Earlobe Keloids with Imiquimod after Tangential Shave Excision

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