Role of sugars in surface microbe–host interactions and
immune reaction modulation
Blackwell Publishing Ltd
David H. Lloyd*, Jacqueline Viac†, Dirk Werling‡,
Christophe A. Rème§ and Hugues Gatto§
*Department of Veterinary Clinical Sciences, Royal Veterinary
College, Hawkshead Campus, North Mymms, Hertfordshire, UK
†INSERM U346, Hôpital Edouard Herriot, Pavillon R, F-69437,
Lyon Cedex 03, France
‡Department of Veterinary Pathology and Infectious Diseases,
Royal Veterinary College, Hawkshead Campus, North Mymms,
Hertfordshire, UK
§Medical Department, Virbac SA, 13e rue LID, BP 27, F-06511,
Carros, France
Correspondence: David H. Lloyd, Department of Veterinary Clinical
Sciences, Royal Veterinary College, Hawkshead Campus, North
Mymms, Hertfordshire, UK. E-mail: [email protected]
What is known about the topic of this paper
• Sugars are vital components of both microbial and
mammalian cells.
• They are involved in cellular communication and govern
microbial virulence as well as host immunity and
inflammation.
• The use of sugars to block microbial adherence and invasion
and to modulate inflammation offers great therapeutic
potential.
What this paper adds to the field of veterinary
dermatology
• This review summarizes current knowledge of carbohydrates and carbohydrate receptors relating to host–
microbe interaction and immune reaction modulation in
the skin.
• It identifies the therapeutic potential in controlling microbial
disease that may be achieved by blocking microbial
virulence mechanisms and modulating inflammation by
means of simple and complex sugars.
Abstract
Sugars in the form of monosaccharides, oligosaccharides,
polysaccharides and glycoconjugates (glycoproteins,
glycolipids) are vital components of infecting microbes
and host cells, and are involved in cell signalling
associated with modulation of inflammation in all
integumental structures. Indeed, sugars are the
molecules most commonly involved in cell recognition
and communication. In skin, they are essential to
epidermal development and homeostasis. They play
important roles in microbial adherence, colonization
and biofilm formation, and in virulence. Two groups of
pathogen recognition receptors, C-type lectins (CTL)
and their receptors (CTLR), and the Toll-like receptors
enable the host to recognize pathogen-associated
molecular patterns (PAMPs), which are mainly glycolipids. The CTLs can recognize a wide variety of bacteria,
fungi and parasites and are important in phagocytosis
and endocytosis. TLRs are expressed on the surfaces
of a variety of cells, including keratinocytes, dendritic
cells, monocytes and macrophages; they play a major
role in innate immunity. Interaction of TLRs with PAMPs
initiates a cascade of events leading to production
of reactive oxygen intermediates, cytokines and
chemokines, and promotes inflammation. Exogenous
sugars can block carbohydrate receptors and competitively displace bacteria from attachment to cells,
including keratinocytes. Thus sugars may provide
valuable adjunctive anti-inflammatory and/or antimicrobial treatment. A promising approach is the use of
a panel of carbohydrate derivatives with anti-adhesive
efficacy against bacteria frequently involved in diseases
affecting skin and other epithelia. More complete
characterization of sugar receptors and their ligands
will provide further keys to use of carbohydrates in
immunomodulation and infection control in skin.
Accepted 23 April 2007
Introduction
The integument provides the essential barrier, which
maintains homeostasis in animals and enables effective
defence against microbial infection. The primary defensive
capacity of the integument is provided by the epithelia of
the respiratory, gastrointestinal and urinogenital tracts and,
in skin, by the epidermis.
The protective function of the epidermis is due to an
integrated array of defence mechanisms incorporating the
physical and chemical properties of the stratum corneum,
its self-cleaning ability through desquamation, the secretions
of the cutaneous glands and substances passing through
the epidermis from the dermis, and the release from cells
within the epidermis of peptides and lipid metabolites which
are antimicrobial and may also inhibit microbial adherence.
Thus, although the skin is constantly exposed to potential
pathogens, such as Staphylococcus intermedius and
Malassezia pachydermatis1,2 infection only occurs when
the normal epidermal defences are disrupted.
In such circumstances, superficial infections may occur
as a consequence of microbial adherence, proliferation
and the production of virulence factors. In addition, biofilm
production by certain organisms may confer special properties on the constituent microbes including enhancement
of virulence and resistance to antimicrobial agents.3–5
Biofilms are created when microbes proliferate to form
dense interacting communities on a solid surface, typically
surrounded by an extracellular polysaccharide slime matrix.
They are dependent on adherence to substrate, commonly
host cells or inert substances such as catheters, the
© 2007 The Authors. Journal compilation © 2007 ESVD and ACVD. 18; 197–204
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Lloyd et al.
availability of appropriate nutrients, including those released
by inflamed and damaged host cells, and quorum sensing
by the microbes.6–8
Sugars and sugar receptors are vital components of the
cellular structures of both infecting microbes and of the
host cells.9,10 They are involved in microbial adherence,
microbial uptake and in cell signalling associated with
modulation of the inflammatory mechanisms in skin. In
the epidermis, modulation of carbohydrate expression
occurs during keratinocyte differentiation, and epidermal
carbohydrates are involved in lipid maturation and the
development of the epidermal barrier.11–13 Sugars are also
involved in protection of the stratum corneum from proteolytic degradation14 and modification of sugar moieties
may be important in epidermal homeostasis, barrier dynamics
and desquamation.15,16 Cell surface glycoproteins are also
involved in intercellular interaction between keratinocytes
and dendritic cells.17
Thus sugars have the potential to interfere with adherence and biofilm formation, and modulate surface barrier
function and inflammatory reactions by the host. This
review examines data supporting the use of simple and
complex sugars in the control of cutaneous infections and
inflammatory disease.
Sugars in cell signalling and host–microbial
interaction
The sugars can be divided into two major subfamilies, the
simple sugars (monosaccharides) and the complex sugars
(oligosaccharides composed of two to 10 and polysaccharides with more than 10 monosaccharide molecules).
The complex sugars link with proteins and fats to form
glycoproteins and glycolipids (glycoconjugates) with a very
broad range of properties. Indeed, sugars are the molecules
most commonly involved in cell recognition and communication. They do this by means of lectins, ubiquitous
complex proteins found in all living organisms that are
able to recognize in a specific and reversible manner
carbohydrates, such as D-galactose, D-mannose, D-fucose,
sialic acid and N-acetyl-galactosamine that are exposed on
cell membranes in the form of glycoproteins, glycolipids or
polysaccharides (Fig. 1). They may be expressed by both
host cells (endogenous lectins) and pathogens (exogenous
lectins), and their expression varies according to the
activity, maturity and differentiation of the cells, and on
the status of cell surface glycoproteins. Thus surface
glycoproteins are important in regulating and promoting
cellular biological and immunological activity.18 However,
lectins do not belong to the immune system, do not catalyse
reactions and their structures remain poorly characterized.
The interaction between microbial agents and the animal
host cell is multivalent. The abundance of carbohydrates in
various forms at the animal cell surface is one reason why
microbes to a large extent have evolved with the ability to
adhere to sugar receptors in an organ-specific manner for
colonization and infection.19
Microbial lectins are glycoproteins that are known to be
important virulence factors involved in specific interactions
with host carbohydrate cell membrane receptors. They
can interact with corresponding sugar moieties located
on cell surfaces and may be blocked by exogenous
198
Figure 1. Diagrammatic representation of the macrophage mannose
receptor (MMR). This type I transmembrane protein exhibits an Nterminal R-type lectin-like domain, which interacts with sulphated
residues on glycoprotein hormones, followed by a fibronectin type II
domain and 8 or 10 C-type lectin-like domains. The MMR is found on
various cell types including macrophages, immature dendritic cells
and human epidermal Langerhans’ cells. It mediates absorption of
antigens expressing mannose, fucose, N-acetyl-glucosamine and
glucose, and facilitates antigen delivery to MHC class I and II molecules. It is Important in host defence including uptake and destruction
of bacteria, fungi and parasites via glycolipid pathogen-associated
molecular patterns (PAMP).
carbohydrates.20 Carbohydrates at bacterial cell surfaces
can also be involved in induction of virulence by promoting
intercellular adhesion among microbial cells during biofilm
formation (Figs 2 and 3).22–24
Adherence, the specific attachment of microorganisms
to epithelial cells (Figs 4–6), is an initial step in the pathogenesis of epithelial tissue infection. Biofilm formation and
the production of capsular polysaccharide slime can also
be important steps in this process and may be controlled
by quorum sensing activity related to cell density.25,26
Bacterial adherence involves different types of lectins
(adhesins), depending on bacterial strain and host cell. In
vitro models thus require appropriately differentiated cells
in order to study pathogen adherence. In the epidermis,
pathogenic bacteria and fungi will bind to corneocytes.27–29
and any alteration of the keratinocyte differentiation
process (e.g. wound healing, inflammation, and defective
permeability barrier) can promote bacterial adherence.
There is evidence that carbohydrates are important
in the pathogenesis of atopic dermatitis and associated
microbial infections. In atopic dermatitis, decreased stratum
corneum ceramide content may cause a defect in the permeability barrier function that helps initiate immunological
© 2007 The Authors. Journal compilation © 2007 ESVD and ACVD.
Sugars in microbe–host interactions
Figure 4. Malassezia pachydermatis cells attached to canine corneocytes held on adhesive tape in an adherence study (crystal violet stain;
image courtesy of Dr R. Bond).
Figure 2. Diagrammatic representation of a bacterial cell. Adhesins
enable attachment to host cells; they may form part of the cell wall
or cell membrane, or be located on fimbriae and pili; they attach to
glycoconjugates on host tissue such as fibrin and fibronectin. Capsular
polysaccharide promotes adherence to host tissues and inert objects,
e.g. catheters, and is involved in biofilm formation; it gives protection
against phagocytosis. Cell wall protein A binds the Fc portion of immunoglobulin inhibiting phagocytosis. Cell wall, red; cytoplasm, yellow.
Figure 5. Staphylococcus intermedius cells attached to canine
corneocytes held on adhesive tape in an adherence study (crystal
violet stain; image courtesy of Dr L. Saijonmaa-Koulumies).
Figure 3. Diagram of the cell wall of Pseudomonas aeruginosa
showing the location of capsular slime and the superficial lipopolysaccharide attached to the outer membrane. The anionic polysaccharide
slime forms the matrix in which the cells become embedded during
biofilm formation, and is able to bind cationic antibiotics and restrict
their penetration. The lipopolysaccharide may also act as a permeability
barrier to antimicrobials. After Lambert.21
reactions and inflammation.30 Pathogenic staphylococci
can colonize the skin of patients suffering from atopic
dermatitis, and pathogenic staphylococci adhere more
readily to corneocytes of atopic humans and dogs than to
corneocytes of normal individuals or to dogs with primary
© 2007 The Authors. Journal compilation © 2007 ESVD and ACVD.
Figure 6. Clusters of Malassezia pachydermatis cells in a clinical
tape strip specimen from canine skin with Malassezia overgrowth.
DiffQuik stain (image courtesy of Dr M-C Cadiergues).
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Lloyd et al.
seborrhoea.31 In man, one factor in this process is the
redistribution of the glycoprotein, fibronectin, to the cornified
layer in atopic dermatitis.32 It is also suggested that peptidoglycan of Staphylococcus aureus directly exacerbates
inflammation in human atopic dermatitis.33 In dogs, the
adherence in vitro to canine corneocytes of certain strains
of M. pachydermatis and S. intermedius has been shown to
be associated with mannosyl-bearing carbohydrate residues
and with trypsin-sensitive proteins or glycoproteins.34–36
Individual-specific sugars involved in adhesion of bacteria
to a number of epithelial tissues were predicted and
identified some time ago.19,37,38 Furthermore, several studies
suggest that occupation of lectins on the bacterial surface
by exogenous sugars can prevent bacterial adherence to
epithelial cells of different tissues.39–41 Thus, the use of
sugars to competitively displace bacteria from their attachment sites on cells would be particularly valuable when
there is antimicrobial resistance.19 Mannose and N-acetylD-galactosamine inhibit the adherence of Escherichia coli
and Pseudomonas aeruginosa to epithelial cells.38 A
combination of D-galactose, D-mannose and L-rhamnose
was found to decrease the adherence of P. aeruginosa to
canine corneocytes by roughly 50%42 and the polysaccharide,
alkyl polyglucoside, reduces adherence of S. intermedius
to canine corneocytes by 48%.43
Pathogen recognition receptors
Complex oligosaccharide structures displayed at microbial
and host cell surfaces, incorporated into the extracellular
matrix and attached to secreted glycoproteins can serve
structural roles, mediate movement of glycoconjugates to
the cell surface or act as markers that mediate cell–cell
and cell–matrix recognition events. The nonstructural roles
of sugars generally require the participation of sugar-binding
lectins.44 Two groups of pathogen recognition receptors
(PRR), the C-type lectins (CTL) and C-type lectin receptors
(CTLR), and the Toll-like receptors (TLR), enable the
host to recognize pathogen-associated molecular patterns
(PAMP), mainly glycolipid structures.45,46 Lectins are often
complex, multidomain proteins but their sugar-binding
activity can usually be ascribed to a single protein module
within the lectin polypeptide.44 Such a module is designated
a carbohydrate-recognition domain (CRD). C-type lectins
and CTLRs contain various CRDs and represent a very
heterogeneous group with members such as the macrophage
mannose receptor (MMR, Fig. 1) and langerin (see http://
www.imperial.ac.uk/research/animallectins/). In recent years,
a variety of these CTLs and CTLRs, such as dectin-1, DCSIGN (CD209), and DEC-205 (CD205), have been intensively
studied in the murine and human systems. The MMR is
the best-characterized PRR to date. Initially identified in
macrophages, it is involved in phagocytosis and endocytosis
and can recognize mannose, fucose, glucose and N-acetylglucosamine, but not galactose, by means of a series of
carbohydrate domains. It is able to recognize a wide range
of bacteria, fungi and parasites through glycolipid PAMPs.
It plays an important role in host defence against fungal
pathogens and is involved in glycoprotein clearance.47 It is
also expressed by immature dendritic cells. Furthermore,
a keratinocyte mannose receptor (KMR) has been recently
described.39 It exhibits similarities but also some differences
200
from the MMR. The KMR has a different molecular mass
and does not exhibit any cross-reactivity with monoclonal
anti-MMR antibody. It resembles the MMR in that it is
Ca2+-dependent and proteolysis sensitive, but it does not
internalize mannose efficiently and is probably not a member
of the endocytic CTLs. Langerin, another member of the
CTLR family, is expressed with Birbeck granules, the specific
intracellular organelles of Langerhans’ cells. Langerin
(CD207) binds and mediates the uptake of sugar-containing
molecules including mannose, fucose and N -acetylglucosamine. It serves to internalize microbial glycolipids
into Birbeck granules where the glycolipids are loaded into
CD1a for presentation to T cells.48
So far, the only CTLR family members that have been
identified in the canine system at the genomic level are
CLEC2B and CLEC4F, and no functional data on these
receptors have been published for the canine system.
However, given their importance in pathogen neutralization49
and in organization of the extracellular matrix, the annotation
of the canine genome will soon be followed by functional
studies.
In addition to CTLR, and often forming complexes with
them, TLRs do not seem to mediate the uptake of PAMPs
but rather stimulate an intracellular signalling cascade.50
TLRs are expressed on the surfaces of a variety of cells,
including epithelial cells, dendritic cells, monocytes and
macrophages. They play a major role in innate immunity
to microbial pathogens and are the subject of intensive
study.51 Interaction of TLRs with their corresponding
PAMPs initiates a rapid cascade of events leading to production of reactive oxygen intermediates, cytokines and
chemokines, and promotes the inflammatory response.
TLRs represent the main PRR for PAMP derived from
gram-positive and gram-negative bacteria, as well as
bacterial CpG motifs (unmethylated CG dinucleotide in
specific base-sequence contexts).52 Sequences for canine
TLRs 2, 4 and 9 have been published, and the presence
of TLR transcripts has been investigated in different
tissues.53–55 Canine peripheral blood neutrophils have
been shown to respond to lipoteichoic acid, a TLR2 ligand,
with the production of interleukin (IL)-8;56 whereas this
is not conclusive evidence that this reaction was TLR2dependent, it clearly indicates that these cells are able to
mount a pro-inflammatory response to a TLR2 ligand.
Interestingly, keratinocytes have been reported to constitutively express TLR2, TLR3, TLR4, TLR5, TLR9 and to
a lesser extent TLR10.57,58 This indicates that they are
capable of responding to bacterial PAMPs, such as protein
A of S. aureus59 which can cause serious damage to the
skin. Injury to the skin, by either intrinsic factors (such as
single nucleotide polymorphisms in the PRR genes) or
extrinsic factors (such as disruption of the healthy skin
integument), can impair the beneficial recognition of
bacterial mono- and polysaccharides.
Recent studies suggest that microbial components
interact with signalling molecules of the TLR family to
transduce signals in various cells, including keratinocytes.
Treatment of keratinocytes with Candida albicans, mannan,
lipopolysaccharide (LPS) and IFN-γ result in cell activation
and increased IL-8 gene expression. This pathogeninduced expression of pro-inflammatory cytokine secretion
is inhibited by anti-TLR2 and anti-TLR4 neutralizing antibodies,
© 2007 The Authors. Journal compilation © 2007 ESVD and ACVD.
Sugars in microbe–host interactions
Figure 7. Diagrammatic representation of a
cytokine bound by its receptor-binding domain
and also recognizing a specific carbohydrate
epitope on an adjacent surface complex via
a lectin (the carbohydrate-binding domain).
After Cebo et al.63
suggesting that TLRs are involved in the signalling process.60
These findings open a new avenue to test carbohydrate
molecules, either to stimulate the production of antimicrobial
substances and/or to exert specific interference with
TLRs.
Immunomodulatory properties of
monosaccharides
Carbohydrate moieties are important sites of interaction
for many lymphocyte functions including natural killer cell
activity, lymphocyte–endothelial cell adhesion and lymphocyte
recirculation. As long ago as 1984, Stankova and RolaPleszezynski demonstrated that alpha-fucose inhibited
human mixed lymphocyte culture reactions and subsequent suppressor cell generation.61 L-rhamnose has been
shown to block splenocyte stimulation by LPS.62 Various
sugars are also components of cytokine receptor sites,
e.g. fucose and mannose, on the lymphocyte surface. These
sugars can provide binding sites for extracellular lectins
thus enabling them to play a role in cytokine-mediated
signal transduction. Recent data indicate that some
cytokines exhibit a carbohydrate recognition domain
localized opposite the receptor binding domain, making
cytokines bi-functional (Fig. 7).63 It is now recognized that
several cytokines, including TNF and IL-1, have lectin-like
activity. For instance, IL-1α and IL-1β exhibit distinct and
specific carbohydrate-binding properties, which could explain
why these two cytokines have different signalling profiles,
and different target cells, despite sharing the same cell
receptors.63
Monosaccharides are able to inhibit the cutaneous
delayed hypersensitivity reaction.64 Locally applied α-Lfucose inhibits the expression of delayed hypersensitivity
response in a model of contact allergy sensitization and
elicitation in mice. Application of α-L-fucose before sensitization has no suppressive effect, suggesting that the
monosaccharide plays a role in the inflammatory phase
only and that it acts locally.65 Recent data also argue for
interesting pharmacological properties of L-fucose in
wound healing and age-related modifications of dermal
fibroblasts through collagen biosynthesis.66
© 2007 The Authors. Journal compilation © 2007 ESVD and ACVD.
It is now recognized that keratinocytes play an important
role in skin immunity by secreting a large number of
cytokines. Keratinocytes express cytokine receptors on
their surfaces, allowing them to respond to their own
cytokine secretions (autocrine response) or to other soluble
factors in their microenvironment. Activated keratinocytes
are directly and indirectly responsible for the recruitment
and local activation of leucocytes. Thus an intricate, cytokinebased signalling network in the epidermis can form the
basis of a cascading inflammatory response in diverse
skin diseases. Keratinocytes also possess the ability to
synthesize and express cell surface moieties characteristic
of effector or accessory cells of the immune system,67
and there is increasing evidence of the ability of sugars to
influence cell-to-cell communication among keratinocytes
and immune system activity.
Thus sugars prepared from purified Aloe polysaccharides
reduce the amount of IL-10 observed in ultravioletirradiated murine keratinocytes.68 During the inflammatory
response, keratinocytes can be induced to express the
cell surface adhesion molecule ICAM-1/CD54 that binds
to its ligand LFA-1 expressed on T cells, contributing to
T-cell epidermotropism. Specific monosaccharides (fucose,
rhamnose), alone or in combination, can reduce IFN-γinduced ICAM-1/CD54 expression on human keratinocytes69
and down-regulate the secretion of proinflammatory
cytokines IL-8 and TNF-α by activated keratinocytes
(unpublished results). Masking of the cell membrane
antigen or cell surface receptor by the sugar treatment is
a likely explanation for these results.
Keratinocytes also have the ability to kill pathogenic
fungi and bacteria by producing a large panel of antimicrobial
substances.60,70 Some of these act by binding to microbial
carbohydrates.71
Conclusions and perspectives
The plasma membrane of mammalian cells contains
numerous microdomains that are essential for cellular
function and are biochemically composed of glycoproteins
and glycolipids, which play a major role in the recruitment
and concentration of molecules involved in cellular signalling
201
Lloyd et al.
and in acquired immune responses. Sugar receptors,
when engaged by microorganisms or particles, represent
signal transducing receptors that can trigger a variety of
responses including secretion of mediators, cytokine
production, and modulation of other cell surface receptors
leading to inflammatory reactions. Conversely, the ability
of exogenous sugars to block these specific receptors or/
and to competitively displace bacteria from their attachment
sites on cells may provide an adjunctive anti-inflammatory
and/or antimicrobial treatment. A promising approach in
cutaneous/epithelial superinfections is the use of a panel
of carbohydrate derivatives displaying anti-adhesive efficacy
against bacteria frequently involved in a number of diseases
affecting the skin and other epithelia.
It would be also of major interest to develop molecules
able to mimic commensal bacterial cell membrane glycoproteins. These commensals are regarded as beneficial for
the host and provide protection by chronically stimulating
epithelial surfaces to express antimicrobial peptides at
levels that kill pathogenic microbes. Such molecules would
specifically stimulate natural defence mechanisms that
regulate the presence of bacteria on skin and epithelial
surfaces, as well as exerting a protective immunomodulating
effect on epidermal cells.
More complete characterization of the structure and
function of sugar receptors and their ligands in the skin
and epithelia would provide a better knowledge of the
relationships between innate and adaptive immunity and
their interaction in defence reactions. Such knowledge
will provide further keys to the use of carbohydrates in
immunomodulation and infection control in skin.
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Résumé Les sucres monosaccharides, oligosaccharides, polysaccharides et glycoconjugués (glycoproteines,
glycolipides) sont des composants vitaux des microbes infectieux et des cellules de l’hôte et sont impliquées
dans le signalement cellulaire associé à la modulation de l’inflammation dans toutes les structures
tégumentaires. En fait, les sucres sont les molécules les plus fréquemment impliquées dans la reconnaissance cellulaire et la communication. Dans la peau, ils sont essentiels au développement épidermique et
à l’homéostasie. Ils jouent des rôles importants dans l’adhérence microbienne, la colonisation et la formation
de biofilms, et pour la virulence bactérienne. Deux groupes de récepteurs, les C-type lectins (CTL) et leurs
récepteurs (CTLR), et les TOLL-like receptors permettent à l’hôte de reconnaître le type moléculaire de
pathogène (PAMPs), qui sont surtout des glycolipides. Les CTL peuvent reconnaître une grande variété de
bactéries, de champignons et de parasites et sont importants pour la phagocytose et l’enfocytose. Les TLRs
© 2007 The Authors. Journal compilation © 2007 ESVD and ACVD.
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sont exprimés à la surface de cellules variées, incluant les kératinocytes, les cellules dendritiques, les
monocytes et les macrophages; ils jouent un rôle majeur dans l’immunité innée. L’interaction des TLRs avec
les PAMPs provoque une cascade d’évènements provoquant la production de réactifs oxygénés, de
cytokines et de chémokines, et facilite l’inflammation. Les sucres exogènes peuvent bloquer les récepteurs
et éliminer les bactéries des cellules, incluant les kératinocytes. Les sucres sont donc des traitements associés
anti-inflammatoires et/ou antimicrobiens. Une approche intéressante est l’utilisation d’un ensemble de
sucres avec une action antiadhésive sur les bactéries les plus souvent impliquées dans les maladies
cutanées. La détermination plus précise des récepteurs aux sucres et de leurs ligands permettra des solutions
futures pour l’utilisation des sucres dans l’immunomodulation et le contrôle de l’infection cutanée.
Resumen Los azúcares en la forma de monosacáridos, oligosacáridos, polisacáridos y glicoconjugados
(glicoproteínas, glicolípidos) son componentes vitales de los microorganismos infecciosos y las células
hospedadoras, y están implicados en las señales celulares asociadas con la modulación de la inflamación
en todas las estructuras tegumentarias. De hecho los azúcares son las moléculas más implicadas en el
reconocimiento y comunicación celulares. En la piel son esenciales para el desarrollo y la homeostasis. Juegan
un papel importante en la adherencia microbiana, colonización y formación de películas biológicas (biofilms)
y virulencia. Dos grupos de receptores de reconocimiento de patógenos, lectinas de tipo C (CTL) y sus receptores
(CTLR), y los receptores tipo TOLL (TLRs), permiten al hospedador reconocer patrones moleculares asociados
a agentes patógenos (PAMPs), que son principalmente glicolípidos. Los CTL pueden reconocer una amplia
variedad de bacterias, hongos y parásitos, y son importantes en la fagocitosis y endocitosis. Los TLRs son
expresados en la superficie de una gran variedad de células, incluidos queratinocitos, células dendríticas,
monocitos y macrófagos, y juega un papel importante en la inmunidad innata. La interacción de los TLRs
con los PAMPs inicia una cascada de procesos que llevan a la producción de intermediarios reactivos de
oxígeno, citoquinas y quimoquinas y promueven la inflamación. Los azúcares exógenos pueden bloquear los
receptores de carbohidratos y desplazar de forma competitiva bacterias de su unión con las células, incluidos
los queratinocitos. Así pues los azúcares pueden proporcionar una ayuda valiosa en el tratamiento antiinflamatorio y/o antimicrobiano. Una estrategia prometedora es el uso de un grupo de derivados de carbohidratos
con propiedades antiadhesivas frente a bacterias implicadas en enfermedades de la piel y otros epitelios.
Una caracterización mas completa de los receptores de azúcares y sus ligandos proporcionará mas claves
en el uso de carbohidratos para el control de la inmunomodulación e infección en la piel.
Zusammenfassung Zucker in der Form von Monosacchariden, Oligosacchariden, Polysacchariden und
Glykokonjugaten (Glykoproteine, Glykolipide) sind lebensnotwendige Komponenten von infektiösen
Mikroben und Wirtszellen und sind am Zell-Signalling beteiligt, welches mit der Modulation der Entzündung
in allen Hautstrukturen assoziiert wurde. In der Tat sind Zucker jene Moleküle, die hauptsächlich bei der
Zellerkennung und Kommunikation involviert sind. In der Haut sind sie essentiell für die epidermale
Entwicklung und Homeostase. Sie spielen eine wichtige Rolle bei der mikrobiellen Anhaftung, Kolonisierung
und Ausbildung von Biofilm und bei der Virulenz. Zwei Gruppen von Rezeptoren, die Krankheitserreger
erkennen, C-type Lectine (CTL) und ihre Rezeptoren (CTLR), und die TOLL-like Rezeptoren, machen es dem
Wirt möglich bestimmte molekulare Strukturen des Pathogens (‘Pathogen-associated molecular patterns’)
(PAMPs), welche hauptsächlich Glykolipide sind, zu erkennen. Die CTL können eine große Variation an
Bakterien, Pilzen und Parasiten erkennen und sind wichtig bei der Phagozytose und Endozytose. TLRs
werden auf der Zelloberfläche zahlreicher Zellen, wie den Keratinozyten, dendritischen Zellen, Monozyten
und Makrophagen exprimiert; sie spielen eine große Rolle bei der angeborenen Immunität. Die Interaktion
von TLRs mit PAMPs initiiert eine Kaskade von Ereignissen, welche zur Produktion von reaktiven Sauerstoffzwischenprodukten, sowie zu Zytokinen und Chemokinen führen und begünstigt die Entzündung.
Exogene Zucker können die Kohlenhydrat Rezeptoren blockieren und konkurrierend Bakterien von der
Anhaftung an Zellen, inklusive Keratinozyten, verdrängen. Daher können Zucker eine wertvolle entzündungshemmende und/oder antimikrobielle Behandlung zur Verfügung stellen. Eine vielversprechende Herangehensweise ist die Verwendung einer Liste von Kohlenhydratderivaten mit antiadhäsiver Wirkung gegen
Bakterien, die häufig bei Krankheiten beteiligt sind, die die Haut und andere Epithelien betreffen. Eine
vollständigere Charakterisierung der Zuckerrezeptoren und ihrer Liganden wird weitere Schlüsse für die
Verwendung von Kohlenhydraten bei der Immunmodulation und Infektionskontrolle der Haut zulassen.
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