Immunization and dermatophytes
Bernard Mignona, Jeremy Tabarta, Aline Baldoa, Anne Mathya, Bertrand Lossona
and Sandy Vermoutb
a
Department of Infectious and Parasitic Diseases,
Parasitology, Faculty of Veterinary Medicine, University
of Lie`ge, Lie`ge and bFederal Agency for Medicinal and
Health Products, Brussels, Belgium
Correspondence to Bernard Mignon, Universite de
Lie`ge, Faculte de Medecine Veterinaire, Departement recent advances in hostdermatophyte relationships that could have implications for
des Maladies Infectieuses et Parasitaires, section
Parasitologie, Boulevard de Colonster 20, 4000 Lie`ge,
Belgium
Tel: +32 4 366 40 99; fax: +32 4 366 40 97;
e-mail: bmignon@ulg.ac.be
Current Opinion in Infectious Diseases 2008,
21:134140
Introduction
Dermatophytosis is a common and clinically multifaceted
fungal skin disease affecting both humans and animals.
Usually, infection is limited to the stratum corneum, hair
or nails. The responsible agents are pathogenic derma-
tophytes, a group of highly specialized filamentous fungi
which are able to invade and digest keratin in vivo.
Despite their superficial localization in skin, they induce
in their hosts a specific immune response, which can
result, though not automatically, in subsequent protec-
tion against reinfection. Besides, the use of live attenu-
ated vaccines has proved to be a valuable mean of control
and even eradication of dermatophytosis in cattle and
fur-bearing animals. The existence of efficient and com-
mercially available vaccines against dermatophytosis is
unique in the field of medical and veterinary mycology.
Indeed, though being the most prevalent fungal diseases,
dermatophytoses remain considerably less studied than
opportunistic mycoses such as aspergillosis and candidia-
sis, including immuno-pathological aspects [1]. During
the past decade, however, there has been a resurgence of
interest in dermatophytes and dermatophytosis leading
notably to the molecular characterization of fungal immu-
0951-7375 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Purpose of review
Despite the availability of effective vaccines for certain animal species, vaccination
against dermatophytosis requires improvement and further development in both animals
and humans. This review provides an update on the current situation and focuses on
future vaccination against the most prevalent of the fungal diseases.
Recent findings
Numerous dermatophytic virulence factors have recently been isolated and
characterized at the molecular level, notably secreted proteases involved in the invasion
of the keratin network. Their precise roles in the different steps of the infectious process
and in immunopathogenesis are being studied, while all aspects of the host immune
response against dermatophytes, including the innate response, are becoming
increasingly documented. In addition, new molecular tools are now available for
studying dermatophytes, which will accelerate research on this topic.
Summary
The growth of knowledge concerning all aspects of the hostdermatophyte relationship
should contribute towards sound strategies for the development of effective and safe
vaccines against dermatophytosis.
Keywords
dermatophyte, immune response, protease, vaccine, virulence factor
Curr Opin Infect Dis 21:134140
2008 Wolters Kluwer Health | Lippincott Williams & Wilkins
0951-7375
nogens and virulence factors. Also, in the wake of recent
discoveries in immunology, including the aspects of
immunity to opportunistic fungal infections [1,2], scat-
tered but interesting progress in the understanding of the
immune response to dermatophytes has been achieved.
This review intends to summarize and comment on the
most recent literature, addressing hostdermatophyte
relationships and focusing mainly on vaccination, fungal
virulence factors, their putative involvement in both the
innate and specific host immune responses and potential
implications for modern and safe vaccination against
dermatophytosis.
Vaccination against dermatophytosis
To date, there is no commercial or standardized vaccine
for preventing or eliminating any fungal infection in
humans, including dermatophytosis. There is, however,
intensive research aiming to develop safe and efficient
antifungal vaccines, but essentially against opportuni-
stic fungal infections affecting immuno-compromised
patients [3]. In contrast to these infections, dermato-
phytoses are not life-threatening and occur most often in

immuno-competent individuals. Except in the case of
geophilic species (e.g. Microsporum gypseum), dermato-
phytes must be considered as obligatory parasitic fungi
because they do not reproduce nor produce macroconidia
and microconidia in the environment, and do not form
part of the normal cutaneous flora. Because of this intrin-
sic characteristic, the development of a useful vaccine
against human dermatophytosis could imply a more clas-
sical approach than against opportunistic mycoses. This
view must, however, be tempered by the fact that some
dermatophytes are so highly adapted to their hosts that
they may cause chronic, and even asymptomatic, infec-
tions, as sometimes observed for Trichophyton rubrum in
humans and Microsporum canis in cats. These mycoses
result from fungal immunomodulation or the existence of
poor Th1 responders [4,5].
Some live vaccines are effective in particular animal
species
The need for a vaccine against human dermatophytosis
remains to be evaluated medically and economically. This
is not the case in animals. Indeed, both the high incidence
of this contagious skin disease and its zoonotic and
economic effects have rendered vaccination highly desir-
able, especially in cattle and cats. To be efficient, vaccina-
tion must prevent the development of clinical lesions and
the transmission to other subjects and avoid contamination
of the environment by infective fungal elements. In this
respect, a remarkable success was obtained in cattle, using
a live vaccine containing microconidia of an attenuated
strain of Trichophyton verrucosum [6]. Large-scale vaccina-
tion programmes carried out in Eastern Europe and
Scandinavia in the past 35 years using this vaccine have
dramatically reduced the incidence of both bovine ring-
worm and concurrent human infections. Protection was
correlated with the induction of an immune response
comparable with that induced by natural infections, which
is a cell-mediated immune response. In fact a Th1
response, as demonstrated by a delayed-type hypersensi-
tivity (DTH) skin reaction, is induced both in naturally
and vaccinated animals. These results prove that vaccina-
tion against dermatophytosis is a realistic strategy for
preventing dermatophytosis. This success story cannot
obviate the lack of knowledge about basic immunology
of dermatophytosis, especially in comparison with the
constantly increasing level of understanding of immune
mechanisms involved in other fungal infections [1].
The efficacy of inactivated vaccines is questionable
Inactivated vaccines have also been developed and are
currently marketed for use notably in cattle, horses and
cats. In cattle and horses, data concerning their efficacy
and the duration of the induced immune response are not
firmly established. One of their theoretical advantages
over live vaccines is their potential use in already dis-
eased animals, which is particularly relevant in veterinary
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Immunization and dermatophytes Mignon et al. 135
medicine. In fact, some inactivated vaccines are mar-
keted not only as a preventive but also as a treatment. We
recently performed a random placebo-controlled double-
blinded study to evaluate the curative efficacy of a
commercial inactivated vaccine against T. verrucosum in
17 naturally infected heifers. Both clinical and mycologi-
cal follow-up was performed every 2 weeks for 5 months.
There was no significant difference between vaccinated
and control animals, the only significant factor affecting
the time-course of the disease being time (B. Losson,
personal communication). These results corroborate the
overall disappointing observations of many practitioners
on the global inefficacy of inactivated vaccines against
dermatophytosis in cattle and horses.
Efficient vaccines for cats are to be developed
Several well conducted studies were performed in the
target species by DeBoer and Moriellos team using
either an experimental cell wall vaccine [7] or a commer-
cially available inactivated crude product of M. canis [8].
These attempts were largely unsuccessful. Interestingly,
their immunization protocols induced no, or a weak
specific cell-mediated immune response, compared with
that induced in self-curing natural infections. These
results were interpreted by the authors as indicative of
the need to develop a subunit vaccine, with clearly
defined composition and immunologic properties, and
affording a high safety degree. In this context, our lab
produced a M. canis keratinolytic exo-antigen, which
proved to be immunogenic both in naturally infected
cats and experimentally infected guinea pigs. Moreover,
in this model, the exo-antigen induced a specific DTH in
animals that had recovered from infection [9]. Sub-
sequently the genes coding for two major proteases of
the exo-antigen a keratinolytic subtilisin (Sub3) [10]
and a keratinolytic metalloprotease (Mep3) [11] were
isolated and recombinant proteins were produced. Exper-
imentally infected guinea pigs were then shown to
develop a lymphoproliferative immune response against
both recombinant Sub3 [12] and Mep3 [13]. Con-
sequently, the protective properties of these immuno-
gens mixed with a Freunds adjuvant were evaluated in
this species. Although each tested immunogen elicited a
significant specific cell-mediated immune response, the
latter was transient, which could account for the absence
of protection conferred by the vaccines against an
epicutaneous challenge [14,15]. In this respect, new
adjuvants should be used to stimulate a strong and
long-lasting Th1 response. The route of administration
should also be reconsidered. Indeed, not only the nature
and the concentration of the immunogen itself, but also
the molecular and cellular context in which it is presented
to the dendritic cells are instrumental to generate an
appropriate Th1 cell immune response inducing active
cellular effectors, macrophages and neutrophils, on
the infection site [1]. Nevertheless, in view of further
 136 Skin and soft tissue infections
experiments, it must be remembered that the in-vivo
experimental vaccine assays are more relevant when
performed in the target species, the cat for M. canis.
Furthermore, to mimic as much as possible a natural
challenge, infection commingling should be considered.
Immunity to dermatophytosis
Even if available data are rather limited, the most recent
literature on active immunization against dermatophytosis
shows that there is a trend to develop safer and more
efficient vaccines than those, attenuated or inactivated,
belonging to the first generation. Although live vaccines
are efficient against some dermatophytes in particular
animal species, they are proscribed for use in humans or
in contact pet animals notably because of a possible
reversion to virulence. As a consequence, scientists essen-
tially focus their studies on isolation, characterization and
subsequent use of major fungal immunogens able to elicit a
specific Th1 response and to stimulate strong memory
T-cell responses. This requires the elucidation of the
innate and specific immune pathways that are associated
both with the various clinical manifestations resulting from
infection of a particular host by a particular dermatophyte
species and with protective vaccination. Additionally, the
identification of the fungal virulence factors and the under-
standing of their role in the first steps of infection, adhesion
and invasion of epidermis, constitute, in our opinion, an
important facet, from a fungal perspective, of the immu-
nopathogenesis of dermatophytosis.
A Th1 cell immune response is needed for protection
In the past decades, numerous studies have shown that
infections by dermatophytes induce a specific immune
response with humoral and cellular components, and that
the efficient and protective response is a cell-mediated
response of the DTH type, characterized mainly by the
action of macrophages and neutrophils as effectors, and
thus by elevated activity of the key cytokines IL-12 and
IFN-g from the Th1 axis. The immune response that is
raised, however, including the degree of inflammation,
varies according to the dermatophyte species, the host
species, and the physiopathological status of the host.
Chronic and recurrent infections with T. rubrum and
M. canis are quite common in humans and cats respect-
ively, without any associated immunodeficiency. Most
often, chronic human infections are correlated with poor
specific DTH, elevated specific IgE and IgG4, and IgE-
mediated immediate hypersensitivity. Clinical and exper-
imental arguments supporting this consensual view about
the duality of the immune response to dermatophytes have
been previously reviewed and discussed [4,5].
A role for humoral immunity?
Even if the role for specific antibodies in host defence
against dermatophytes is questionable, their potential
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usefulness cannot be ruled out. Indeed, in some models
of other fungal infections, such as disseminated candi-
diasis, protection was shown to be elicited by the pro-
duction of specific antibodies, while experiments using
other models of the same disease pointed out the Th1
cell-mediated immune response to be the critical arm of
protection [16]. In fact, there is increasing evidence that
both protective and non-protective inhibiting/blocking
antifungal antibodies coexist [17], and that protection can
be conferred by the induction of an appropriate antibody
response or by the use of specific monoclonal antibodies
(mAbs) [3]. This is exemplified by the recent develop-
ment of an original glyco-conjugate vaccine, based on a
single b-glucan of algal origin, which was protective
against both candidiasis and aspergillosis in rodents,
through the induction of anti-b-glucan antibodies [18].
The importance of protective antibodies against specific
fungal antigens, including secreted proteases known as
virulence factors, was also demonstrated in a model of
vaginal candidiasis in rats [19]. This study showed
notably that genetically engineered antibody variable
domains against the secreted aspartyl protease Sap2, an
enzyme which is involved in adherence to and invasion of
the host tissues, had protective effects by inhibiting yeast
adherence to vaginal epithelial cells. In dermatophytosis,
further studies should also be performed to assess if
naturally or vaccine induced antibodies can be protective.
As dermatophytes invade the most superficial layers of
the skin, their secreted antigens, such as keratinolytic
proteases [20], could be the most important targets of the
host immune system. Besides, M. canis infection in cats or
guinea pigs induces antibodies against the proteases
Mep3 [13] and, to a lesser extent Sub3 [21]. Interestingly,
mAbs against Sub3 significantly decreased the adherence
of M. canis arthroconidia (A. Baldo, unpublished data) in a
model of feline dermatophytosis using a recently devel-
oped in-vitro reconstructed feline epidermis (RFE) [22].
Though preliminary, these studies indicate that the role
of antibodies in dermatophytosis must be revisited, as
this is progressively performed in other fungal infections.
A pivotal role for innate immunity in dermatophytosis
During recent years, research about innate antifungal
immunity was very productive leading to important dis-
coveries, again concerning mainly opportunistic infec-
tions [23,24]. A comprehensive overview of the innate
immune mechanisms involved in the different clinical
presentations of dermatophytosis would, however, be
instrumental, notably because the receptors, the path-
ways and the cells which are involved have an instructive
role on cells of the adaptive immune system, and thus on
the induction or not of a Th1 cell mediated protective
response [1,23]. It is largely beyond the scope of this
brief review to give details about general or specific
concepts of innate immunity. Some recent studies, how-
ever, dealing with this topic and dermatophytosis are

mentioned below as they provide some insights, which
may be pieces of the puzzle to be solved for this field.
Keratinocytes are the first epidermal cells that the der-
matophytes encounter during the infection process.
These cells have a pivotal role in the modulation of
the host immune response [25]. Indeed, upon exposure
to dermatophytes they can produce a broad spectrum of
cytokines [26], including IL-8, a potent chemo-attractant
for neutrophils, which can kill dermatophytes, and the
proinflammatory TNF-a [27]. Dermatophyte species
differ, however, in their ability to induce cytokine pro-
duction by keratinocytes. The zoophilic species stimu-
late the production of pro-inflammatory cytokines by
human keratinocytes better than anthropophilic ones
[26,28], and this correlates with the clinical aspects
observed in both types of infection. Such a dichotomic
view, however, is probably too simplistic, as we observed
that feline keratinocytes, which are exposed to live or
heat-inactivated arthroconidia of a single dermatophyte
strain (M. canis IHEM 21239) produce different cytokinic
responses (J. Tabart, personal communication). In fact,
we have no idea yet about the dermatophyte components
that interact with keratinocytes, nor the cellular receptors
involved. This should be investigated both because
keratinocytes are known to express several types of
pattern recognition receptors (PRRs), including Toll-like
receptors (TLRs) and mannose receptors, and because
the dermatophytic virulence factors are currently being
characterized at the molecular level. It should be remem-
bered that in most dermatophyte infections, the fungal
elements are confined to the cornified skin layers. Con-
sequently, though living keratinocytes are used in most
in-vitro experiments, they are in contact in vivo with
secreted fungal antigens rather than structural ones. This
is the reason why we are currently studying the role of
keratinocytes in the induction of the anti-M. canis
immune response using a fully differentiated, horny layer
containing RFE [22] and the available recombinant
secreted fungal proteases such as Sub3 and Mep3
[13,14]. Besides cytokines, human keratinocytes also
secrete antimicrobial peptides (AMP), cathelicidins and
defensins with potential antifungal activity. Their role in
skin defence against dermatophytes was suggested by
several authors who showed that human b-defensin [29]
and cathelicidin LL-37 [30] are either fungistatic or
fungicidal in vitro against T. rubrum and that their expres-
sion is upregulated in vivo in tinea corporis.
There is no doubt that dendritic cells, especially epider-
mal Langerhans cells, are antigen-presenting cells
that are instrumental for both initiation and modulation
of the adaptative antidermatophyte immune response.
Recently, dectin-2, a C-type lectin-like receptor consti-
tutively expressed by mature dendritic cells, such as
Langerhans cells, was shown to be a PRR for fungi,
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Immunization and dermatophytes Mignon et al. 137
including Microsporum andouinii and T. rubrum, and to
bind preferentially to hyphae rather than conidia, leading
in fine to the upregulated secretion of proinflammatory
cytokines such as TNF-a [31]. In contrast, upon pha-
gocytosis by macrophages, T. rubrum conidia induce the
secretion of the anti-inflammatory cytokine IL-10, while
other factors related to enhancement of a relevant pro-
tective immune response are downregulated: class II
major histocompatibility complex, CD54 and CD80
co-stimulation molecules, nitric oxide and IL-12 [32].
Campos et al. [32] also showed that phagocytosis of
T. rubrum conidia by macrophages was inhibited by both
cell wall mannans and exo-antigen. This is in agreement
with previously reported postulates stating that the cell
wall mannans possess immuno-inhibitory properties
potentially responsible for T. rubrum chronic dermato-
phytosis in humans. In fact, it appears that some immu-
nomodulation depends on which dermatophyte factors
are produced in the course of infection, but also how they
are detected by the host. As an example, a yeast cell wall
derivative, zymosan, considered to be an inducer of pro-
inflammatory cytokines, was recently demonstrated to
induce regulatory dendritic cells and immunological tol-
erance through a TLR2 and dectin-1 mediated IL-10
release [33]. The relevance of these regulatory mech-
anisms in vivo is strengthened by the recent demon-
stration that, in a mouse model of systemic candidiasis,
TLR2 has a direct role in the control of immune
responses, and also the issues of infections, through
the control of expansion and function of regulatory
T cells [34].
Besides keratinocytes and dendritic cells, neutrophils are
important cells in innate antidermatophyte immunity. In
mice, they were shown to accumulate as early as 46 h
after experimental infection with T. mentagrophytes [35],
after adherence of conidia to the corneocytes, during the
germination phase. Additionally, it is generally admitted
that neutrophils are, in addition to macrophages, the
effector cells allowing in fine, via the Th1-dependent
inflammatory response, the elimination of a dermatophy-
tic infection. The role of neutrophils in Th1 cell acti-
vation through several mechanisms including dendritic
cells instruction [36,37], however, remains to be
addressed in dermatophytosis. Such a role for neutrophils
has been demonstrated in oral candidiasis, another super-
ficial fungal infection [38].
Virulence factors of dermatophytes
As mentioned above, the characterization of fungal
pathogenic factors has been one of the main fields of
research on dermatophytes during the last 5 years. It
undoubtedly constitutes an important topic to further
study the immuno-pathogenesis of dermatophytosis and
to develop prophylactic strategies. Indeed, virulence
 138 Skin and soft tissue infections
factors can be expressed all along the infection process to
modulate the host immune response and therefore can be
important immunogens. Structural antigens of dermato-
phytes, including cell wall glycoproteins, remain poorly
or even not characterized. Most efforts have focused
primarily on secreted proteases. The keratinolytic,
immunogenic, in-vivo-produced Sub3 and Mep3 of
M. canis were the first to be fully characterized at the
molecular level [1013]. They belong to large protein
families that were further characterized in several der-
matophyte species [39,40]. Their role in fungal adhesion
to keratinocytes was recently hypothesized [41] and is
currently investigated in our laboratory (see above).
These endoproteases are thought to be involved in the
digestion of hard keratinized substrates in cooperation
with exoproteases such as aminopeptidases and dipepti-
dyl-peptidases (Dpp) that have been isolated from
T. rubrum [42] and M. canis (S. Vermout, unpublished
data). The action of all these proteases is likely to be
preceded by sulphitolysis of keratin, a mechanism which
was recently shown to be controlled by a sulphite efflux
pump encoded by the SSU1 gene [20]. Other regulatory
genes include DNR1 [43] of M. canis and PACC of
T. rubrum [44] both encoding a transcription factor which
is involved in regulation of the keratinolytic activity.
There are several examples that the molecular charac-
terization of the putative dermatophyte pathogenic
factors is an important step towards a comprehensive
understanding of the immunopathogenesis of dermato-
phytosis. Sub6 from T. rubrum [40] and the orthologue of
T. rubrum Dpp5 [42] in Trichophyton tonsurans were
demonstrated to be the previously described Tri r2
[45] and Tri t4 [46] allergens respectively, two proteins
capable of inducing dual immune responses in humans
[5]. Also, the well known different inflammatory reactions
induced by different dermatophyte species in a given
host species could be related to a differential expression
of genes encoding homologous secreted enzymes, includ-
ing proteases [47,48]. Further elucidation of the patho-
genic role of the proteins which are currently being
characterized will undoubtedly benefit from the recent
development of several new tools. Functional investi-
gation of genes is now available, as gene disruption via
homologous recombination has been attained in the
dermatophytes T. rubrum [44,49] and M. canis [43].
RNA interference technology constitutes a realistic
alternative tool, as it has been successfully applied in
M. canis to downregulate the expression of genes coding
for Sub3 and Dpp4 [50]. The generation of expressed
sequence tags (ESTs) [51,52] and high-throughput
methods developed in T. rubrum for the analysis of
transcriptomes the use of cDNA microarrays [5356]
and for the analysis of secreted proteomes [47] will
probably also be helpful to investigate the hostfungus
relationship. Besides genetic tools, relevant ex-vivo or
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
in-vitro infection models, such as RFE for M. canis
dermatophytosis [22], are also needed, especially as they
will allow the evaluation of the role of the putative fungal
virulence factors on the innate host immune system. As a
result, new prophylactic strategies for the control of
dermatophytosis could emerge.
Conclusion
Unfortunately, dermatophytosis has been understudied
compared to opportunistic mycoses during the last
20 years. There is, however, a resurgence of interest in
both dermatophytes and dermatophytic infection. In
particular, several potential fungal virulence factors have
been characterized at the molecular level. The elucida-
tion of the role of the currently and future isolated
pathogenic factors in the hostfungus relationship is
necessary. This ongoing work will undoubtedly contrib-
ute to a better understanding of the immunopathogenesis
of dermatophytosis, as will the identification of host cells,
cell receptors and cytokine pathways, notably those
involved in appropriate innate and thus protective
specific immune responses.
Acknowledgements
The authors are grateful to Professor M. Monod and Dr J.P. Bouchara
for their helpful comments on the manuscript. They also thank
Dr D. OBrien for his advice and suggestions.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:
 of special interest
 of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 201).
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This is an excellent review on innate immunity to fungi, focusing mainly on
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IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens
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25 Sugita K, Kabashima K, Atarashi K, et al. Innate immunity mediated by
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This elegant study showed that, in mice, activation of Langerhans cells by CpG via
TLR9 occurs only in the presence of keratinocytes. This supports the role of
keratinocytes in the modulation of the skin specific immune response.
26 Shiraki Y, Ishibashi Y, Hiruma M, et al. Cytokine secretion profiles of human
keratinocytes during Trichophyton tonsurans and Arthroderma benhamiae
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28 Tani K, Adachi M, Nakamura Y, et al. The effect of dermatophytes on cytokine
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This study confirmed that dermatophytes are able to induce, by keratinocytes, the
production of IL-8, a potent chemo-attractant for neutrophils.
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Immunization and dermatophytes Mignon et al. 139
29 Jensen JM, Pfeiffer S, Akaki T, et al. Barrier function, epidermal differentiation,
 and human beta-defensin 2 expression in tinea corporis. J Invest Dermatol
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An interesting investigative study was conducted on alterations of epidermal
differentiation, barrier functions, and secretion of antimicrobial peptides occurring
in human skin infected by Trichophyton rubrum.
30 Lopez-Garcia B, Lee P, Gallo R. Expression and potential function of
 cathelicidin antimicrobial peptides in dermatophytosis and tinea versicolor.
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This study demonstrated the in-vitro antifungal activity of the antimicrobial peptides
cathelicidin LL-37 and CRAMP on Trichophyton species. The authors also report
an increase of the expression of LL-37 in human epidermis infected with T. rubrum,
suggesting a role for the cathelicidins in skin defence against dermatophytes.
31 Sato K, Yang X, Yudate T, et al. Dectin-2 is a pattern recognition receptor for
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This important study showed for the first time an interaction between dermatophytes
and a pattern recognition receptor (PRR). The PRR dectin-2 on dendritic cells binds
differentially to conidia and hyphae of T. rubrum. This suggests that, as observed for
opportunistic fungi, the peculiar dermatophytic structure interacting with a peculiar
cell receptor is of major importance for the subsequent generated immune response.
32 Campos M, Russo M, Gomes E, Almeida S. Stimulation, inhibition and death
 of macrophages infected with Trichophyton rubrum. Microbes Infect 2006; 8:
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This provides an insight into the putative cellular and molecular mechanisms of
immuno-modulation that could be exerted by dermatophytes in chronic infections.
33 Dillon S, Agrawal S, Banerjee K, et al. Yeast zymosan, a stimulus for TLR2 and
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tolerance. J Clin Invest 2006; 116:916928.
The authors provide a demonstration that a supposed pro-inflammatory fungal
component (zymosan) can induce regulatory dendritic cells and immune tolerance
via both TLR2 and dectin-1.
34 Sutmuller R, den Brok M, Kramer M, et al. Toll-like receptor 2 controls expan-
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This sophisticated study showed that TLR2 triggering by pathogen-associated
molecular patterns present on or secreted by infectious organisms, such as
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35 Hay R, Calderon R, Mackenzie C. Experimental dermatophytosis in mice:
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This is a clear, concise and well illustrated review on how neutrophils and dendritic
cells interact with each other, and how these interactions and the production of
TNF-a by neutrophils induce maturation of dendritic cells and instruct them to
polarize T cells towards Th1 cells.
38 Schaller M, Boeld U, Oberbauer S, et al. Polymorphonuclear leukocytes
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39 Jousson O, Lechenne B, Bontems O, et al. Multiplication of an ancestral gene
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Targeted gene disruption mediated by homologous recombination was obtained
for the first time in a dermatophyte.
44 Ferreira-Nozawa M, Silveira H, Ono C, et al. The pH signaling transcription
 factor PacC mediates the growth of Trichophyton rubrum on human nail in
vitro. Med Mycol 2006; 44:641645.
The authors present an interesting insight into the molecular regulation of the in-
vitro keratinolytic activity of a dermatophyte, showing that disruption of the gene
encoding PacC, a putative pH signalling transcription regulator of T. rubrum,
decreases the fungal growth on isolated human nails.
45 Woodfolk J, Sung S, Benjamin D, et al. Distinct human T cell repertoires
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 140 Skin and soft tissue infections
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protein profiles of different dermatophyte species in different culture media
(see Giddey et al. [48]).
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50 Vermout S, Tabart J, Baldo A, et al. RNA silencing in the dermatophyte
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greatest advantage of this technique over gene disruption is the possibility to
inhibit several genes at the same time, which would be particularly helpful
to investigate the large protease gene families from dermatophytes.
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51 Wang L, Ma L, Leng W, et al. Analysis of the dermatophyte Trichophyton rubrum
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52 Yang J, Chen L, Wang L, et al. TrED: the Trichophyton rubrum Expression
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This is a considerable work intended to be a comprehensive resource and
platform to assist functional genomic studies in dermatophytes (see references
[5356]). Further transcriptome expression patterns analysis will be more
informative, as soon as the complete genome sequences from dermatophytes
are available.
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