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Pathogenesis of tinea

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DOI: 10.1111/j.1610-0387.2010.07481.x Review Article 1

Pathogenesis of tinea
Jochen Brasch
Department of Dermatology, Venereology and Allergy, University Clinic of Schleswig-Holstein, Campus Kiel,
Kiel, Germany

JDDG; 2010 • 8 Submitted: 30.4.2010 | Accepted: 27.5.2010

Keywords Summary
• dermatophytes Dermatophytes are hyphomycetes that can degrade keratin. This puts them in
• enzymes a position to cause infections of the keratin-containing superficial skin. The
• inflammation resulting clinical picture is called tinea. The pathogenesis and course of tinea is
• keratinocytes decisively determined by pathogen-related factors and by the defense mecha-
• epidermal barrier nisms of the host. An infection starts with an adherence of fungal propagules,
• immunity followed by the formation of hyphae that can spread within the tissue. This
process is accompanied by a release of fungal enzymes and other pathogenic
factors. Next keratinocytes are activated, the epidermal barrier is destroyed,
epidermal proliferation is enhanced and defensins are expressed within the epi-
dermis. In addition, innate and specific immune responses are initiated, involv-
ing neutrophilic granulocytes, macrophages, antibodies and T cells. The cellular
mechanisms are thought to be crucial for healing. Special conditions apply to
nail infections, because within nail plates the fungi are not accessible to effec-
tive defense mechanisms, as well as to infections of hair follicles that contain
specific concentrations of steroid hormones. Dermatophytes that penetrate into
the dermis can cause granulomatous inflammatory reactions and systemic
immune reactions are supposed to be a trigger of so-called id reactions.

Tinea
Tinea or dermatophytosis are terms used
to denote skin infections caused by der-
matophytes. Dermatophytes are hy-
phomycetes that (in their perfect form)
are classified among the Arthrodermat-
aceae. The increasing use of genetic tests
in recent years has resulted in many vari-
eties that formerly were considered as
separate dermatophyte species are today
assigned to recognized species, so that
their number has really become manage-
able (Table 1–3) [1]. All dermatophytes
are in principle capable of degrading ker-
atin in the stratum corneum, hair and
nails. They can therefore cause infections
of superficial keratin-containing tissue
layers in humans. Anthropophilic species
(Table 1) obligatorily infect humans,
zoophilic species (Table 2), in contrast,
primarily are transmitted under suitable
conditions from their host animal di-
rectly or indirectly to humans. Geophilic
species (Table 3) degrade keratin in the
ground, but can occasionally, usually fol-
lowing traumatic inoculation, cause in-
fections in humans.
When a dermatophyte infects the skin,
genes of the pathogen relevant for the in-
fection are up-regulated, mycotic viru-
lence factors are released and inflamma-
tory defense reactions of the host are set
in motion [2, 3]. Penetration of the der-
matophytes into the dermis and upper
subcutis especially occurs via invasion of
the hair follicle, but deeper tissue layers or
visceral organs are usually not involved.
Penetration of dermatophytes into the
epidermis leads to a host response. This
depends both on the dermatophyte
(species, perhaps even strain) [4] and on
host defenses [5]. Zoophilic and geophilic
dermatophyte species usually elicit more
intense inflammatory reactions than
anthropophilic species (Table 1) [6]. In
the affected patient age, sex, immune
status and probably also genetic factors
determine the defense reaction [6, 7].

© The Author • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010 JDDG | 2010 (Band 8)
2 Review Article Pathogenesis of tinea

Table 1: Anthropophilic dermatophytes. Table 3: Geophilic dermatophytes.

With worldwide distribution • Trichophyton ajelloi

• Trichophyton rubrum • Trichophyton eboreum
Some T.-rubrum varieties with limited distribution exist: • Trichophyton flavescens
- the former Trichophyton megninii (Portugal, Spain, Sardinia, Burundi) • Trichophyton gloriae
- var. kanei (North America, Europe, Africa) • Trichophyton phaseoliforme
- var. krajdenii (North America, Europe) • Trichophyton terrestre
- var. raubitschekii (Asia, Mediterranean region, South Africa, South America) • Trichophyton thuringiense
• Trichophyton interdigitale (anthropophilic strains) • Trichophyton vanbreuseghemii
• Trichophyton tonsurans • Microsporum cookei
• Epidermophyton floccosum • Microsporum fulvum
• Microsporum audouinii • Microsporum gypseum
• Microsporum racemosum
With special areas of distribution
• Trichophyton schönleinii (Eurasia, North Africa)
• Trichophyton violaceum (Eastern Europe, North Africa, Central America)
- the former Trichophyton gourvilii (West and Central Africa) directly via alteration of epidermal dif-
- the former Trichophyton soudanense (Africa) ferentiation to a disturbance of the epi-
- the former Trichophyton yaoundei (Central and Southeast Africa) dermal barrier [14].
• Microsporum ferrugineum (Asia, Eastern Europe, Africa) In addition to enzymes, further poten-
• Trichophyton concentricum (Pacific Islands, Southeast Asia, Central America) tially pathogenic mycotic factors probably
play a role in dermatophyte invasion.
These include xanthomegnin as a der-
matophyte toxin, mannans as immuno-
Table 2: Zoophilic dermatophytes with main hosts. suppressive factors [15], hemagglutinins
and factors that cooperatively can induce
hemolytic reactions [16]. Substances with
• Trichophyton erinacei (hedgehogs)
antibiotic effects produced by dermato-
• Trichophyton mentagrophytes (rodents, among others)
phytes [17] are possibly important for the
• Trichophyton interdigitale, zoophilic strains (rodents, among others)
fungi to assert themselves in the face of
• Trichophyton simii (monkeys)
synchronous bacterial colonization.
• Trichophyton equinum (horses)
• Trichophyton verrucosum (cattle, among others)
The role of keratinocytes
• Microsporum amazonicum (rats)
The stratum spinosum with its ker-
• Microsporum canis (cats, dogs, among others)
atinocytes is the front line of vital cells
• Microsporum gallinae (owls and other birds)
confronted by the fungus in dermato-
• Microsporum nanum (pigs)
phyte infection of the glabrous skin. Ker-
• Microsporum persicolor (voles and other rodents)
atinocytes themselves participate directly
• Microsporum praecox (horses)
in dermatophyte defense and, in addi-
tion, activate further cells via released cy-
tokines. They therefore play a key role in
Keratinocytes, defense cells, antimicro- trifugally especially in the lower layers of the initial response to tinea. Ker-
bial factors as well as unspecific and spe- the stratum corneum (Figure 1). During atinocytes express Toll-like receptors
cific immune response are involved in germination various fungal genes that (TLR) that can recognize pathogens
defense against pathogens, with these encode for mycotic proteins are activated (pattern recognition receptors). Via these
mechanisms interacting. [9]. UV exposure might possibly direct receptors signals activating the unspecific
the direction of growth of the hyphae immune response can be triggered. The
Initiation of infection into the depth [10]. corresponding ligands on the surface of
The first step in infection is the inocula- Numerous enzymes released by the der- the fungi are presumably species-de-
tion of fungal elements capable of germi- matophytes during growth allow them to pendent “pathogen-associated molecular
nation into the skin or at least adherence degrade and utilize keratins and other patterns” (PAMPs). Even if not yet de-
of such elements to the stratum corneum proteins as well as lipids and DNA tected, it can be assumed that dermato-
[8]. Defects of the stratum corneum, oc- [11–13]. To which extent certain en- phytes can also express such ligands. The
clusion and maceration facilitate this. zymes are produced after activation of interaction with the dermatophyte fur-
When vital fungal elements (usually the respective genes depends greatly on ther results in a significant increase in
arthrospores) attach long enough to the the supply of nutrients [12, 13]. The en- proliferation of the keratinocytes
stratum corneum, germination takes zymatic degradation of substrate con- (Figure 2), to a disturbance of their own
place, hyphae develop that spread cen- tributes directly and presumably also in- keratin pattern (Figure 2) and to a grave

JDDG | 2010 (Band 8) © The Author • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010
Pathogenesis of tinea
Figure 1: Biopsy of lesional tinea, PAS-stain. Spreading hyphae are visible within the lower stratum
corneum.
Figure 2: Biopsy of lesional tinea, immunostaining for Ki 67. Proliferation of basal keratinocytes is
clearly enhanced.
alteration of their “cornified envelope”,
which is as a consequence functionally
damaged (Figure 4) [14]. The epidermal
barrier is distinctly reduced which can be
measured as a strong increase in transepi-
dermal water loss (Figure 5). Lesional
keratinocytes in tinea express defensins
as antimicrobial peptides. Human beta-
defensin 2 was recently detected im-
munohistochemically (Figure 6) [14,
18]. Keratinocytes (and mononuclear
cells of the infiltrate) release multiple in-
© The Author • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010
flammatory cytokines in tinea. In addi-
tion to interferon-␥ especially TNF-␣,
IL-1␤, IL-8 and IL-16 appear to be
important for the inflammatory tissue
reaction [19, 20]. At least in vitro the
spectrum of cytokines released by the
keratinocytes after stimulation by der-
matophytes obviously depends on the
activating dermatophyte species. In
interaction with Arthroderma benhamiae
this was markedly greater than with
Trichophyton tonsurans [20].
Review Article 3
Nonspecific defenses
As the skin surface is never sterile, der-
matophytes also come into contact with
bacteria immediately. Interactions be-
tween dermatophytes and bacteria have
not yet been studied extensively, but
Pseudomonas aeruginosa can inhibit
growth of Trichophyton rubrum and Tri-
chophyton mentagrophyes [21]. Possibly, a
certain bacterial flora may – in the face
of an intact epidermis – prevent the de-
velopment of tinea and thus contribute
to nonspecific defense mechanisms. The
fixation of dermatophytes in the stratum
corneum at any rate counteracts the
markedly increased epidermal prolifera-
tion (Figure 2) [14], which accelerates
the desquamation of fungal elements.
Certain mannans of Trichophyton
rubrum possess inhibitory effects on pro-
liferation. Transferrin can inhibit fungal
growth by binding iron while various
fatty acids in the skin have direct anti-
fungal effects [22]. Neutrophilic granu-
locytes and macrophages as unspecific
defense cells migrate into affected skin.
These cells are attracted by complement-
dependent and complement-independ-
ent mechanisms as well as by low molec-
ular weight chemotactic factors [23] and
can damage or kill dermatophytes.
Lipid-like substances of dermatophytes
consisting of compounds composed of
urea with two unsaturated fatty acids
(Figure 7) can activate phagocytes in
vitro [24, 25]. These substances must be
further studied. Additionally, altered
specific receptors of natural killer cells
and increased CD14-positive monocytes
are observed in patients with tinea [26].
Phagocytes can react to dermatophytes
with an “oxidative burst” and the release
of cytokines such as TNF-␣. The clash
between macrophages and dermato-
phytes can result in death of the fungal
cell or the macrophage [23]. Possibly, the
binding of dermatophyte components to
dendritic cells initiates unspecific de-
fense mechanisms [27].
The specific immune reaction
The specific immune system is involved
in the pathogenesis of tinea with the pro-
duction of antibodies and the activation
of specific defense cells. Therefore both
humoral immune responses as well as de-
layed cellular reactions can occur. In var-
ious dermatophyte species various anti-
gens both in the mycelium and in
arthrospores have been identified [2, 28]
JDDG | 2010 (Band 8)
4 Review Article
Figure 3: Biopsy of lesional tinea, immunostaining for keratin 14. In contrast to normal skin this ker-
atin is also expressed in cell layers of the upper epidermis.
Figure 4: Biopsy of lesional tinea, immunostaining for filaggrin. In contrast to normal skin there is
only focal staining with this marker of the cornified envelope within the stratum granulosum in tinea.
and some of these antigens can elicit dif-
ferent immune responses. For example, a
subtilase of Trichophyton rubrum can re-
sult in an immediate-type reaction as
well as delayed reactions with different
T cells being involved [29]. Similarly a
protein from Trichophyton tonsurans can
result in release by T cells of cytokines in
the pattern of a humoral or as in delayed
immune reaction. A function of the “pat-
tern-recognition receptors” of phago-
cytes have not yet been convincingly
JDDG | 2010 (Band 8)
demonstrated in tinea, but probably toll-
like receptors such as dectin-1 and
dectin-2 play a role in the recognition of
dermatophytes as pathogens [5].
In patients with tinea under suitable
conditions, diverse antibodies towards
dermatophytes can be detected in the
blood and tissue. Nevertheless, such a
Th2-associated humoral immune re-
sponse offers no protection against der-
matophytes [5]; an immediate-type reac-
tion towards dermatophytes appears
© The Author • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010
Pathogenesis of tinea
rather to be associated with persistent in-
fections [2]. Likewise, elevated serum
levels of specific IgE, particularly found
in tinea patients with atopy, have no
protective effect against dermatophytes
and their pathogenetic relevance is un-
clear [30].
Dendritic cells within the skin are found
both in the epidermis and the dermis.
The epidermal dendritic cells (Langer-
hans cells) are an integral part of the
outer protective barrier of the human or-
ganism. They are essential for the recog-
nition of various noxious agents includ-
ing fungi, and the activation of
lymphocytic defense is decisively shaped
by them. Just as dendritic cells in other
tissues they have a watchdog function
and determine the first phase of the spe-
cific immune reaction. In tinea Langer-
hans cells migrate to the site of infection
where they are then found in increased
numbers in tissue [31]. The binding of
dendritic cells to keratinophilic fungi
possibly occurs via the expression of the
lectin CD-SIGN on the surface of these
cells [32]. For this purpose Langerhans
cells can express Toll-like receptors and
thus link unspecific defense and selective
immune response including maturation
of dendritic cells, cytokine release and
lymphocyte activation. Dendritic cells
possess as a further pathogen-recogniz-
ing receptor DC-HIL, which can be acti-
vated by dermatophyte ligands and thus
up-regulate their antigen presentation,
but simultaneously also decrease T-cell
activation. Lymphocytes are not consti-
tutionally present in the epidermis, but
migrate into affected skin in tinea and
are involved in pathogen defense [33].
Besides neutrophilic granulocytes and
macrophages predominantly CD4-posi-
tive T cells are found in lesional dermis
(Figure 8). A specific delayed T cell-me-
diated immune reaction develops in
tinea, which can be demonstrated by a
positive trichophytin test and is a deci-
sive factor for healing of the infection [5,
15, 34, 35]. The pathophysiology of the
delayed T cell reaction in tinea resembles
that in allergic contact dermatitis. The
detection of IFN-␥ in tinea lesions also
suggests the activation of Th1 cells [35]
as does the release of IFN-␥ and cell acti-
vation detectable in the form of CD30
expression [36]. Volunteers infected
with Trichophyton mentagrophytes devel-
oped a positive trichophytin reaction
within 14 days. Immunization against
Pathogenesis of tinea Review Article 5

Figure 7: Chemical structure of a lipid-like

chemotaxin, composed of urea and palmitoleic
acids (bis-palmitoleic urea).

Figure 5: Transepidermal water loss in lesional tinea and healthy skin in g/m2/h. The transepidermal
water loss is markedly enhanced in lesional tinea as compared to normal skin (n = 16, p < 0.0001).

Figure 8: Biopsy of lesional tinea, immunostain-

ing for CD4. The inflammatory infiltrate
includes a considerable amount of CD4-positive
T cells.

CD4+CD25+ regulatory T cells in the

Figure 6: Biopsy of lesional tinea, immunostaining for human beta-defensin 2. Marked expression
within the upper stratum corneum.
dermatophyte infections has to date only
been developed for farm animals; in cat-
tle this leads to a certain degree of cellu-
lar immune protection [37]. Besides im-
munostimulatory factors, Trichophyton
rubrum also produces immunosuppres-
sive mannans. Such mannans and fur-
ther exoantigens of Trichophyton rubrum
can reduce phagocytosis of Trichophyton
rubrum conidia by macrophages [23].
Effects of the location
Tinea can affect any area of the body sur-
face and its course is always determined
by the local conditions. Occlusion and
maceration in intertriginous areas offer
more favorable points of entry and op-
portunity for growth than the free skin.
Two special “ecotopes” differ from the
rest of the body surface: the nails and the
hair follicle, especially on the scalp and
beard.
Fungal infections of the nails by der-
matophytes belong to the most common
infections. The mature nail plate con-
tains no vital cells and has no circulation.
If the dermatophyte succeeds in pene-
trating this niche it can hardly come into
contact with defense cells or hematoge-
nous antimicrobial agents. Thus, in
many cases a permanent infection of the
nail without a tendency for self-healing
results. It is true that in patients with
onychomycosis a higher percentage of
peripheral blood was recently measured
than in healthy subjects and indications
exist for a genetic disposition [38, 39];
the significance of these findings is yet
unclear. In principle, the fungus can be
eliminated if the nail grows distally more
rapidly than the fungus penetrates proxi-
mally, but this quasi mechanical fungus
rejection is rarely successful. Especially in
older persons and in the presence of
trophic disturbances nail growth is sim-
ply too slow. It is still unknown if other
physiologic mechanisms exist to remove
dermatophytes from nails or to kill them
in this location. At any rate onychomy-
coses caused by dermatophytes are al-
most always chronic and hardly inflam-
matory infections.
A further special habitat for dermato-
phytes is the hair follicle. It determines
the peculiarities of tinea capitis or bar-
bae. Originating from the infundibular
follicular epithelium various patterns of
hair involvement can develop depending
on the responsible dermatophyte species.
With primary penetration of the hair

© The Author • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010 JDDG | 2010 (Band 8)
6 Review Article
shaft with endothrix hair colonization
hardly inflammatory infections can de-
velop, as the pathogen similar to the nail
plate remains relatively isolated. When
in contrast the follicular epithelium is
penetrated and destroyed, this rupture
always results in suppurative and granu-
lomatous courses [40]. The follicular ep-
ithelium of the hair and adjoining seba-
ceous glands form a functional unit that
is under hormonal control and con-
tributes decisively to the endocrine func-
tion of the skin. Due to the production
and metabolism of steroid hormones
that occurs here a special milieu is cre-
ated and diverse steroid hormones can
have different effects on the growth of
dermatophytes [41–44]. The fact that
tinea capitis predominantly affects chil-
dren and is rare after puberty might be
associated with the dramatic changes in
follicular hormone concentrations dur-
ing puberty.
Hair follicles can serve as points of entry
for dermatophytes into the subcutis. Sub-
cutaneous dermatophytoses are indeed
rare, but do occur, for example, after deep
rupture of a hair follicle. In such cases
usually a granulomatous inflammatory
reaction develops from which necrotic
material which may contain fungal ele-
ments can empty [45]. Neutrophilic
granulocytes and macrophages are rou-
tinely involved and presumably a specific
immune reaction also, but data on subcu-
taneous infection hardly exist. This is all
the more true for extremely rare systemic
infections by dermatophytes that have
been observed in bone, the CNS, lymph
nodes and other organs [46].
Dermatophytid?
Cells of the peripheral blood and cells of
the skin can react to components of der-
matophytes [35, 47–49]. Mononuclear
cells in the blood of tinea patients can re-
lease IFN-␥ after stimulation with der-
matophyte components and elevated
TNF-␣ serum levels were measured in
tinea patients [34, 49]. Circulating anti-
bodies towards dermatophyte antigens
were also found in the peripheral blood.
It appears possible in principle that such
cells and factors after gaining access to
the peripheral blood might cause cuta-
neous reactions even in nonlesional skin
in patients. These would constitute in-
fection-associated but sterile distant re-
actions that could be termed dermato-
phytid [50]. <<<
JDDG | 2010 (Band 8)
Conflicts of interest
None.
Correspondence to
Prof. Dr. Jochen Brasch
Department of Dermatology, Venereology
and Allergy
University Clinic of Schleswig-Holstein,
Campus Kiel
Schittenhelmstraße 7
D-24105 Kiel, Germany
Tel.: +49-431-5971-507
Fax: +49-431-5971611
E-mail: jbrasch@dermatology.uni-kiel.de
References
1 Brasch J. Dermatophytenspezies. „Neue“
Taxonomie und „neue“ Taxa. Hautarzt
2008; 59: 971–9.
2 Vermout S, Tabart J, Baldo A, Mathy
A, Losson B, Mignon B. Pathogenesis
of dermatophytosis. Mycopathologia
2008; 166: 267–75.
3 Brasch J. Current knowledge of host
response in human tinea. Mycoses
2009; 52: 304–12.
4 Tani K, Adachi M, Nakamura Y, Kano
R, Makimura K, Hasegawa A, Kanda
N, Watanabe S. The effect of dermato-
phytes on cytokine production by hu-
man keratinocytes. Arch Dermatol Res
2007; 299: 381–7.
5 Almeida SR. Immunology of dermato-
phytosis. Mycopathologia 2008; 166:
277–83.
6 Brasch J. Erreger und Pathogenese von
Dermatophytosen. Hautarzt 1990; 41:
9–15.
7 Brasch J. Kutane Entzündungsreaktion
am Beispiel mykotischer Infektionen.
Hautarzt 1990; 41 Suppl. X: 13–5.
8 Duek L, Kaufman G, Ulman Y, Berdi-
cevsky I. The pathogenesis of dermato-
phyte infections in human skin sec-
tions. J Infect 2004; 48: 175–80.
9 Yang L, Wang L, Peng J, Yu L, Liu T,
Leng W, Yang J, Chen L, Zhang W,
Zhang Q, Qi Y, Jin Q. Comparison
between gene expression of conidia and
germinating phase in Trichophyton ru-
brum. Sci China C Life Sci 2007; 50:
377–84.
10 Brasch J, Menz A. UV-Susceptibility
and negative phototropism of dermato-
phytes. Mycoses 1995; 38: 197–203.
11 Viani FC, Dos Santos JI, Paula CR,
Larson CE, Gambale W. Production of
extracellular enzymes by Microsporum
© The Author • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010
Pathogenesis of tinea
canis and their role in its virulence.
Med Mycol 2001; 39: 463–8.
12 Brasch J, Martins BS, Christophers E.
Enzyme release by Trichophyton ru-
brum depends on nutritional conditi-
ons. Mycoses 1991; 34: 365–8.
13 Brasch J, Zaldua M. Enzyme patterns
of dermatophytes. Mycoses 1994; 37:
11–6.
14 Jensen JM, Pfeiffer S, Akaki T, Schroe-
der JM, Kleine M, Neumann C,
Proksch E, Brasch J. Barrier function,
epidermal differentiation and human
␤-defensin 2 expression in tinea
corporis. J Invest Dermatol 2007; 127:
1720–7.
15 Dahl MV, Grando SA. Chronic derma-
tophytosis: what is special about
Trichophyton rubrum? Adv Dermatol
1994; 9: 97–109.
16 Schaufuss P, Brasch J, Steller U. Der-
matophytes can trigger cooperative
(CAMP-like) haemolytic reactions.
Brit J Dermatol 2005; 153: 584–90.
17 Lappin-Scott HM, Rogers ME, Adlard
MW, Holt G, Noble WC. High-perfor-
mance liquid chromatographic identifi-
cation of betalactam antibiotics produ-
ced by dermatophytes. J Appl Bacteriol
1985; 59: 437–41.
18 Kawai M, Yamazaki M, Tsuboi R,
Miyajima H, Ogawa H, Tsuboi R.
Human beta-defensin-2, an antimicro-
bial peptide, is elevated in scales collec-
ted from tinea pedis patients. Int J Der-
matol 2006; 45: 1389–90.
19 Nakamura Y, Kano R, Hasegawa A,
Watanabe S. Interleukin-8 and tumor
necrosis factor alpha production in hu-
man epidermal keratinocytes induced
by Trichophyton mentagrophytes. Clin
Diagn Lab Immunol 2002; 9: 935–7.
20 Shiraki Y, Ishibashi Y, Hiruma M, Nis-
hikawa A, Ikeda S. Cytokine secretion
profiles of human keratinocytes during
Trichophyton tonsurans and Arthro-
derma benhamiae infections. J Med
Microbiol 2006; 55: 1175–85.
21 Treat J, James WD, Nachamkin I,
Seykora JT. Growth inhibition of
Trichophyton species by Pseudomonas
aeruginosa. Arch Dermatol 2007; 143:
61–4.
22 Brasch J, Friege B. Dicarboxylic acids
affect the growth of dermatophytes in
vitro. Acta Dermato-Venereologica
1994; 74: 347–50.
23 Campos MR, Russo M, Gomes E,
Almeida SR. Stimulation, inhibition
and death of macrophages infected
 Pathogenesis of tinea
with Trichophyton rubrum. Microbes
Infect 2006; 8: 372–9.
24 Kahlke B, Brasch J, Christophers E,
Schröder JM. Dermatophytes contain a
novel lipid-like leukocyte activator
(LILA). J Invest Dermatol 1996; 107:
108–12.
25 Schröder JM, Häsler R, Grabowsky J,
Kahlke B, Mallet AI. Identification of
diacylated ureas as a novel family of
fungus-specific leukocyte-activating pa-
thogen-associated molecules. J Biol
Chem 2002; 277: 27887–95.
26 Gazit R, Hershko K, Ingbar A,
Schlesinger M, Israel S, Brautbar C,
Mandelboim O, Leibovici V. Immuno-
logical assessment of familial tinea cor-
poris. J Eur Acad Dermatol Venereol
2008; 22: 871–4.
27 Chung JS, Yudate T, Tomihari M,
Akiyoshi H, Cruz PD Jr, Ariizumi K.
Binding of DC-HIL to dermatophytic
fungi induces tyrosine phosphorylation
and potentiates antigen presenting cell
function. J Immunol. 2009; 183:
5190–8.
28 Kopecek P, Weigl E, Raska M. Detec-
tion of antigens in mycelial and in
arthoconidial phases of Trichophyton
mentagrophytes. Folia Microbiol 1998;
43: 702–6.
29 Woodfolk JA, Sung SS, Benjamin DC,
Lee JK, Platts-Mills TA. Distinct hu-
man T cell repertoires mediate imme-
diate and delayed-type hypersensitivity
to the Trichophyton antigen, Tri r 2.
J Immunol 2000; 165: 4379–87.
30 Palma-Carlos ML, Palma-Carlos AG.
“In vivo” and “in vitro”: tests in the dia-
gnosis of trichophyton allergy. Eur Ann
Allergy Clin Immunol 2007; 39:
328–32.
31 Brasch J, Martens H, Sterry W. Langer-
hans cell accumulation in chronic tinea
pedis and pityriasis versicolor. Clinical
and Experimental Dermatology 1993;
18: 329–32.
© The Author • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010
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32 Serrano-Gómez D, Leal JA, Corbi
AL. DC-SIGN mediates the binding
of Aspergillus fumigatus and keratino-
philic fungi by human dendritic
cells. Immunobiology 2005; 210:
175–83.
33 Brasch J, Sterry W. Immunophenotypi-
cal characterization of inflammatory
cellular infiltrates in tinea. Acta
Dermato-Venereologica (Stockhholm)
1992; 72: 345–7.
34 Koga T, Shimizu A, Nakayama J. Inter-
feron-gamma production in peripheral
lymphocytes of patients with tinea pe-
dis: comparison of patients with and
without tinea unguium. Med Mycol
2001; 39: 87–90.
35 Koga T. Immune response in dermato-
phytosis. Nippon Ishinkin Gakkai Zas-
shi 2003; 44: 273–5.
36 Murphy M. CD30-positive mononuclear
cells in tinea corporis (dermatophytosis).
Mycoses 2008; 52: 182–6.
37 Mignon B, Tabart J, Baldo A, Mathy A,
Losson B, Vermout S. Immunization
and dermatophytes. Curr Opin Infect
Dis 2008; 21: 134–40.
38 Kaya TI, Eskandari G, Guvenc U,
Gunes G, Tursen U, Burak Cimen MY,
Ikizoglu G. CD4+CD25+ Treg cells
in patients with toenail onychomycosis.
Arch Dermatol Res. 2009; 301:
725–9.
39 Faergemann J, Correia O, Nowicki R,
Ro BI. Genetic predisposition – under-
standing underlying mechanisms of
onychomycosis. J Eur Acad Dermatol
Venereol 2005; 19 Suppl. 1: 17–9.
40 Arenas R, Toussant S, Isa-Isa R. Kerion
and dermatophytic granuloma. Myco-
logical and histopathological findings
in 19 children with inflammatory tinea
capitis of the scalp. Int J Dermatol
2006; 45: 215–9.
41 Brasch J, Gottkehaskamp D. The effect
of selected human steroid hormones
upon the growth of dermatophytes
Review Article 7
with different adaptation to man. My-
copathologia 1992; 120: 87–92.
42 Brasch J, Flader S. Human androgenic
steroids affect growth of dermatophytes
in vitro. Mycoses 1996; 39: 387–92.
43 Brasch J. Hormones, fungi and skin.
Mycoses 1997; 40 Suppl.1: 11–6.
44 Brasch J, Flader S, Roggentin P, Wudy
S, Homoki J, Shackleton CHL, Sippell
W. Metabolismus von Dehydroepiand-
rosteron durch Epidermophyton flocco-
sum. Mycoses 2002; 45 (Suppl.1):
37–40.
45 Chastain MA, Reed RJ, Pankey GA.
Deep dermatophytosis: report of 2 ca-
ses and review of the literature. Cutis
2001; 67: 457–62.
46 Marconi VC, Kradin R, Marty FM,
Hospenthal DR, Kotton CN. Dissemi-
nated dermatophytosis in a patient
with hereditary hemochromatosis and
hepatic cirrhosis: case report and review
of the literature. Medical Mycology
2010; 48: 518–27.
47 Di Silveria A, Zeccara C, Serra F, Mosca
M, Ubezio S, Merlini C, Fietta A. Spe-
cific and non-specific parameters of the
host defence system in patients with su-
perficial fungal infections. Mycoses
1995; 38: 453–8.
48 Koga T, Ishizaki H, Matsumoto T, Hori
Y. Cytokine production of peripheral
blood mononuclear cells in dermato-
phytosis patient in response to stimula-
tion with trichophytin. J Dermatol
1993; 20: 441–3.
49 Gazit R, Hershko K, Ingbar A, Schle-
singer M, Israel S, Brautbar C, Mandel-
boim O, Leibovici V. Immunological
assessment of familial tinea corporis. J
Eur Acad Dermatol Venereol 2008; 22:
871–4.
50 Romano C, Rubegni P, Ghilardi A,
Fimiani M. A case of a bullous tinea
pedis with dermatophytid reaction
caused by Trichophyton violaceum.
Mycoses 2006; 49: 249–50.
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