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Hintergrund und Ziele: In Europa sind Infektionen mit Mycobacterium (M.) marinum selten. Wir führten eine retrospektive Studie durch, um klinisches Spektrum sowie Diagnostik, Therapie und Ergebnisse von M.-marinum-Infektionen unter praxisnahen Bedingungen zu analysieren. Patienten und Methodik: In der Datenbank des Universitätsklinikums Würzburg wurden zwischen 1998 und 2018 18 Patienten mit M.-marinum-Infektionen identifiziert. Ergebnisse: Zwölf Betroffene berichteten über eine Exposition gegenüber Zierfischaquarien oder Teichen. Sechzehn Patienten präsentierten Hautläsionen an den oberen Extremitäten. Es wurden keine invasiven Infektionen beobachtet. Der durchschnittliche Zeitraum bis zur Diagnosestellung betrug 15 Wochen. Bei 14 Patienten ergab die Histologie eine granulomatöse Entzündung. In 16 Fällen gelang der kulturelle Nachweis. Die meisten Patienten erhielten eine Antibiotika-Monotherapie (14/18), in vier Fällen wurde eine Kombinationstherapie verabreicht. Die Behandlung (mediane Dauer von 10 Wochen) war bei 13 Patienten erfolgreich. Fünf Patienten stellten sich im Therapieverlauf nicht wieder vor. Schlussfolgerungen: Unsere retrospektive Analyse von M.-marinum-Infektionen an einem tertiären Referenzzentrum in Deutschland zeigte eine erhebliche zeitliche Verzögerung in der Diagnosestellung und belegt die Bedeutung von mikrobiologischer Kultur, PCR und Histologie. Eine Monotherapie mit Clarithromycin (anstelle von Doxycyclin) erwies sich als geeignet, während die Behandlung bei immunsupprimierten oder -geschwächten Patienten und bei ausgedehnten Befunden durch eine Kombinationstherapie ergänzt wurde.

Acitretin is a systemic retinoid that is used in dermatology for treatment of various inflammatory and especially hyperkeratotic diseases. Elevation of liver enzymes may occur occasionally but normally resolves spontaneously, at the latest after termination of acitretin. However, it can very rarely develop into a life-threatening adverse event including drug-induced liver injury (DILI). A 45-year-old man with classical pityriasis rubra pilaris, a frequently severe, inflammatory skin disease, was started on acitretin. After a seemingly harmless elevation of transaminases, a few weeks after initiation of acitretin, the patient experienced a dramatic course of liver injury with hepatic jaundice though acitretin was stopped immediately. Eventually, laboratory values recovered upon high-dose oral prednisolone therapy. Prescribing physicians should keep in mind that acitretin might induce severe liver injury. Even after termination of acitretin laboratory values should be monitored for a while in order to recognize symptomless but harmful drug-induced liver injury in time.

Tinea capitis describes a dermatophyte infection of scalp and hair that predominately occurs in children. The diagnostic workup includes microscopic examination, culture and/or molecular tests. Treatment is guided by the specific organism involved and should consist of systemic agents as well as adjuvant topical treatment. The aim of the present update of the interdisciplinary German S1 guidelines is to provide dermatologists, pediatricians and general practitioners with a decision tool for selecting and implementing appropriate diagnostic and therapeutic measures in patients with tinea capitis. The guidelines were developed based on current international guidelines, in particular the 2010 European Society for Pediatric Dermatology guidelines and the 2014 British Association of Dermatologists guidelines, as well as on a review of the literature conducted by the guideline committee. This multidisciplinary committee consists of representatives from the German Society of Dermatology (DDG), the German-Speaking Mycological Society (DMykG), the German Society for Hygiene and Microbiology (DGHM), the German Society of Pediatric and Adolescent Medicine (DGKJ) and the German Society for Pediatric Infectious Diseases (DGPI). The Division of Evidence-based Medicine (dEBM) provided methodological assistance. The guidelines were approved by the participating medical societies following a comprehensive internal and external review., Die Tinea capitis ist eine durch Dermatophyten hervorgerufene, vor allem im Kindesalter auftretende Mykose der behaarten Kopfhaut. Die Diagnostik erfolgt mittels mikroskopischer, kultureller und/oder molekularer Methoden. Die Therapie sollte systemisch und begleitend topisch erfolgen und ist abhängig von dem jeweiligen Erreger. Das Ziel des Updates dieser interdisziplinären deutschen S1-Leitlinie ist es, vor allem Dermatologen, Kinderärzten und Allgemeinmedizinern eine Entscheidungshilfe für die Auswahl sowie Durchführung einer geeigneten und suffizienten Diagnostik und Therapie für Patienten mit Tinea capitis zur Verfügung zu stellen. Die Leitlinie wurde unter Berücksichtigung aktueller internationaler Leitlinien, insbesondere der Leitlinien der European Society for Pediatric Dermatology 2010 sowie der British Association of Dermatologists 2014 und den Ergebnissen einer Literaturrecherche durch die Leitlinienkommission erstellt. Diese Kommission ist multidisziplinär und besteht aus Vertretern der Deutschen Dermatologischen Gesellschaft (DDG), der Deutschsprachigen Mykologischen Gesellschaft (DMykG), der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM), der Deutschen Gesellschaft für Kinder- und Jugendmedizin e.V. (DGKJ) und der deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI). Methodisch wurde die Leitliniengruppe durch die Division of Evidence-based Medicine (dEBM) begleitet. Die Leitlinie wurde nach einem umfangreichen internen und externen Review durch die beteiligten Fachgesellschaften freigegeben.

Background and Objectives In Europe, infections with Mycobacterium (M.) marinum are rare. We conducted a retrospective single-center study to assess the clinical spectrum of M. marinum infection and its diagnosis, treatment and outcome under real-world conditions. Patients and Methods Eighteen patients presenting with M. marinum infections between 1998 and 2018 were identified in the data warehouse of the University Hospital Würzburg and considered for detailed analysis. Results Twelve patients reported aquatic exposure. In 16/18 cases the upper extremities were affected. No invasive infections were detected. Mean time to diagnosis was 15 weeks. Histology revealed granulomatous inflammation in 14 patients while mycobacterial cultures were positive for M. marinum in 16 cases. Most patients received antibiotic monotherapy (14/18) while combination therapy was administered in four cases. Treatment (with a median duration of 10 weeks) was successful in 13 patients. Five patients were lost to follow-up. Conclusions Our retrospective analysis of M. marinum infections at a German tertiary referral center revealed a considerable diagnostic delay and the relevance of microbiological culture, PCR and histology for diagnosis. Monotherapy with clarithromycin (rather than doxycycline) appeared as a reasonable treatment option while immunosuppressed or -compromised patients and those with extended disease received combination therapy.

Tinea capitis describes a dermatophyte infection of scalp and hair that predominately occurs in children. The diagnostic workup includes microscopic examination, culture and/or molecular tests. Treatment is guided by the specific organism involved and should consist of systemic agents as well as adjuvant topical treatment. The aim of the present update of the interdisciplinary German S1 guidelines is to provide dermatologists, pediatricians and general practitioners with a decision tool for selecting and implementing appropriate diagnostic and therapeutic measures in patients with tinea capitis. The guidelines were developed based on current international guidelines, in particular the 2010 European Society for Pediatric Dermatology guidelines and the 2014 British Association of Dermatologists guidelines, as well as on a review of the literature conducted by the guideline committee. This multidisciplinary committee consists of representatives from the German Society of Dermatology (DDG), the German-Speaking Mycological Society (DMykG), the German Society for Hygiene and Microbiology (DGHM), the German Society of Pediatric and Adolescent Medicine (DGKJ) and the German Society for Pediatric Infectious Diseases (DGPI). The Division of Evidence-based Medicine (dEBM) provided methodological assistance. The guidelines were approved by the participating medical societies following a comprehensive internal and external review.

HINTERGRUND Die Tinea capitis ist die haufigste Dermatomykose des Kindesalters. Das Erregerprofil zeigt unterschiedliche geographische Verteilungsmuster und variiert im Laufe der Zeit. PATIENTEN UND METHODIK Zwischen 1990-2014 an der Wurzburger Universitatsklinik fur Dermatologie erhobene Daten von 150 Patienten mit mykologisch gesicherter Tinea capitis wurden hinsichtlich Alter, Geschlecht und Erregerspektrum analysiert und uber zwei Zeitraume von jeweils 12,5 Jahren miteinander verglichen. ERGEBNISSE Obwohl eine Tinea capitis am haufigsten bei Kindern der Altersgruppe zwischen 0 und 5 Jahren diagnostiziert wurde, lag der Anteil betroffener Erwachsener mit 16 % hoher als bislang berichtet. Der zoophile Dermatophyt Microsporum canis konnte am haufigsten als Erreger der Tinea capitis identifiziert werden, jedoch war ein Anstieg von Infektionen mit den anthropophilen Pilzen Trichophyton tonsurans und Trichophyton rubrum zu verzeichnen. Tendenziell sank der Anteil zoophiler im Verhaltnis zu den anthropophilen Erregern. Im zeitlichen Verlauf zeigte sich eine zunehmende Heterogenitat des Erregerspektrums: Dermatophyten wie Trichophyton soudanense und Trichophyton violaceum, Trichophyton anamorph von Arthroderma benhamiae sowie Trichophyton schoenleinii und Microsporum audouinii konnten erstmalig bzw. nach langer Zeit wieder erneut isoliert werden. SCHLUSSFOLGERUNGEN Wenngleich Microsporum-canis-Infektionen noch dominieren, sind zunehmend anthropophile Erreger nachzuweisen. Angesichts des unerwartet hohen Anteils von Erwachsenen sollte eine Tinea capitis in allen Altersgruppen differenzialdiagnostisch in Betracht gezogen werden.

Background Tinea capitis is the most common type of dermatomycosis in children. Its pathogen profile shows geographic variations as well as temporal shifts. Patients and methods Data from 150 patients with mycologically confirmed tinea capitis treated at the Department of Dermatology, University Hospital Wurzburg, between 1990 and 2014 were analyzed with respect to gender, age, and pathogen spectrum. Two time periods, each 12.5 years long, were compared. Results Although tinea capitis was most frequently diagnosed in children between the ages of 0 and 5, the percentage of adults (16 %) was higher than previously reported. The zoophilic dermatophyte Microsporum canis was most frequently identified as the causative agent of tinea capitis. However, there was a rise in infections caused by the anthropophilic fungi Trichophyton tonsurans and Trichophyton rubrum, and also a trend towards a lower percentage of zoophilic versus anthropophilic pathogens. Over the course of time, we observed an increase in the diversity of the pathogen spectrum. Dermatophytes such as Trichophyton soudanense, the Trichophyton anamorph of Arthroderma benhamiae, Trichophyton schoenleinii, and Microsporum audouinii were isolated either for the first time or for the first time after a long hiatus. Conclusions Although Microsporum canis infections still predominate, there has been an increase in anthropophilic pathogens. Given the unexpectedly high percentage of adults, tinea capitis should be included in the differential diagnostic considerations in all age groups.

Summary Background The data concerning frequency and relevance of the toxin Panton-Valentine leukocidin (PVL) in skin infections caused by Staphylococcus aureus is controversial. The objective of the study was the identification of the role of the toxin in community-acquired skin infections caused by S. aureus. Patients and Methods We performed a retrospective analysis of 112 patients with the diagnosis of skin infections caused by S. aureus. Frequency of PVL was investigated by PCR for the lukSF gene. Risk factors and severity of the disease were analyzed. Furthermore, spa typing was done in 55 of the isolated S. aureus. Results PVL occurred in 45 % of patients with skin infections caused by methicillin-susceptible S. aureus; methicillin-resistant strains were positive in 63 %. Mean age was 30.9 years in PVL-positive infections and thus statistically highly significantly lower than in PVL-negative infections. There was no correlation between presence of PVL and severity and course of skin infections or presence of special risk factors. The spa types showed a high variability in PVL-positive as well as in PVL-negative strains. Conclusions In our study the PVL status of S. aureus isolated from skin infections was neither correlated with methicillin-resistance nor with the severity of disease. Remarkably, PVL-positive S. aureus strains appeared to be more frequent in younger than in older patients. Our results demonstrate that routine determination of PVL status is not required since the outcome has no diagnostic or therapeutic consequences in daily dermatological practice.

Tinea capitis is the most common type of dermatomycosis in children. Its pathogen profile shows geographic variations as well as temporal shifts.Data from 150 patients with mycologically confirmed tinea capitis treated at the Department of Dermatology, University Hospital Würzburg, between 1990 and 2014 were analyzed with respect to gender, age, and pathogen spectrum. Two time periods, each 12.5 years long, were compared.Although tinea capitis was most frequently diagnosed in children between the ages of 0 and 5, the percentage of adults (16 %) was higher than previously reported. The zoophilic dermatophyte Microsporum canis was most frequently identified as the causative agent of tinea capitis. However, there was a rise in infections caused by the anthropophilic fungi Trichophyton tonsurans and Trichophyton rubrum, and also a trend towards a lower percentage of zoophilic versus anthropophilic pathogens. Over the course of time, we observed an increase in the diversity of the pathogen spectrum. Dermatophytes such as Trichophyton soudanense, the Trichophyton anamorph of Arthroderma benhamiae, Trichophyton schoenleinii, and Microsporum audouinii were isolated either for the first time or for the first time after a long hiatus.Although Microsporum canis infections still predominate, there has been an increase in anthropophilic pathogens. Given the unexpectedly high percentage of adults, tinea capitis should be included in the differential diagnostic considerations in all age groups.

Die Tinea capitis ist die häufigste Dermatomykose des Kindesalters. Das Erregerprofil zeigt unterschiedliche geographische Verteilungsmuster und variiert im Laufe der Zeit.Zwischen 1990-2014 an der Würzburger Universitätsklinik für Dermatologie erhobene Daten von 150 Patienten mit mykologisch gesicherter Tinea capitis wurden hinsichtlich Alter, Geschlecht und Erregerspektrum analysiert und über zwei Zeiträume von jeweils 12,5 Jahren miteinander verglichen.Obwohl eine Tinea capitis am häufigsten bei Kindern der Altersgruppe zwischen 0 und 5 Jahren diagnostiziert wurde, lag der Anteil betroffener Erwachsener mit 16 % höher als bislang berichtet. Der zoophile Dermatophyt Microsporum canis konnte am häufigsten als Erreger der Tinea capitis identifiziert werden, jedoch war ein Anstieg von Infektionen mit den anthropophilen Pilzen Trichophyton tonsurans und Trichophyton rubrum zu verzeichnen. Tendenziell sank der Anteil zoophiler im Verhältnis zu den anthropophilen Erregern. Im zeitlichen Verlauf zeigte sich eine zunehmende Heterogenität des Erregerspektrums: Dermatophyten wie Trichophyton soudanense und Trichophyton violaceum, Trichophyton anamorph von Arthroderma benhamiae sowie Trichophyton schoenleinii und Microsporum audouinii konnten erstmalig bzw. nach langer Zeit wieder erneut isoliert werden.Wenngleich Microsporum-canis-Infektionen noch dominieren, sind zunehmend anthropophile Erreger nachzuweisen. Angesichts des unerwartet hohen Anteils von Erwachsenen sollte eine Tinea capitis in allen Altersgruppen differenzialdiagnostisch in Betracht gezogen werden.

Meningococcal lipopolysaccharide (LPS) is of crucial importance for the pathogenesis of invasive infection. We show that sialylation and elongation of the alpha-chain effectively shields viable unencapsulated Neisseria meningitidis from recognition by human dendritic cells (DC). In contrast, beta- and gamma- chain of the LPS carbohydrate moiety play only a minor role in the interaction with DC. The protective function of the LPS for the bacteria can be counteracted in vivo by phase variation of the lgtA gene encoding LPS glycosyltransferase A. Capsule expression protects N. meningitidis efficiently from recognition and phagocytosis by DC independent of the LPS structure. Despite the significant impact of LPS composition on the adhesion and phagocytosis of N. meningitidis no differences were found in terms of cytokine levels secreted by DC for IL1-beta, IL-6, IL-8, TNF-alpha, IFN-gamma and GM-CSF. However, significantly lower levels of the regulatory mediator IL-10 were induced by encapsulated strains in comparison to isogenic unencapsulated derivatives. IL-10 secretion was shown to depend on phagocytosis because poly alpha-2,8 sialic acid did not influence IL-10 secretion. The use of truncated LPS isoforms in vaccine preparations can therefore not only result in attenuation but also in more efficient targeting of DC.

Morphological plasticity of Candida albicans is a major virulence factor. Using pH-dependent dimorphism we show, that human dendritic cells (DC) recognize filamentous forms and blastoconidia of a virulent C. albicans isolate (strain SC5314). Heat inactivated and viable blastoconidia are rapidly phagocytosed by human DC. However, viable yeast cells start to filament inside the DC at later stages of infection, leading to penetration and loss of cellular integrity. The cytokine burst of human DC induced upon contact with Candida is dominated by the granulocyte-activating, chemotactic factor IL-8 and the proinflammatory mediator TNF-alpha. Blastoconidia induce markedly lower cytokine levels than filamentous forms. Whereas IL-8 secretion is mainly cell mass dependent, release of TNF-alpha, a major proinflammatory cytokine, is clearly dependent on the morphology of Candida.

The unusual case of a 29-year-old woman with tinea manus caused by infection due to Trichophyton erinacei is described. The patient presented with marked erosive inflammation of the entire fifth finger of her right hand. Mycological and genomic diagnostics resulted in identification of T. erinacei as the responsible pathogen, which had been transmitted by a domestic African pygmy hedgehog, Atelerix albiventris. Upon prolonged treatment with topical and systemic antifungal agents skin lesions slowly resolved. This case illustrates that the increasingly popular keeping of extraordinary pets such as hedgehogs may bear the risk of infections with uncommon dermatophytes.

Summary We describe a woman presenting primarily with slowly progressing scarring alopecia. Course, symptoms, and clinical picture were highly suggestive for lichen planus. But mycological investigations revealed that cicatricial alopecia was caused by a specific infection with Trichophyton schoenleinii running a chronic course with minimal skin inflammation.

@ Background: Systemic mastocytoses are a group of diseases, which are characterized by accumulation and unusual growth of mast cells infiltrating two different organs or types of tissue. Two case reports are introduced.□ Classification: According to the new WHO classification of 2000, mastocytoses are separated into cutaneous and systemic mastocytoses. Systemic mastocytosis is subdivided into an indolent course with good prognosis and four subgroups with poor prognosis (systemic mastocytosis with associated clonal hematologic non-mast-cell disease, aggressive systemic mastocytosis, mast cell leukemia, and mast cell sarcoma). □ Genetics: Systemic mastocytoses are clonal disorders of mast cells and their progenitor cells, which may show point mutations ofthe protooncogene c-kit. This gene codes for the stem cell receptor (CD117). □ Therapy: Therapy of systemic mastocytosis depends on patient's symptoms. There is no known cure of the disease. Besides diet and avoidance of skin irritations, symptoms are treated with H 1 - or H 2 -blockers, steroids, leukotriene receptor antagonists, and PUVA therapy. If patients suffer from systemic reactions such as hypotension or syncope, epinephrine solution should be prescribed for emergency use.

Bacteria-mediated transfer of plasmid DNA into mammalian cells (bactofection) is a potent approach to express plasmid-encoded heterologous proteins (protein antigens, toxins or enzymes) in a large set of different cell types including phagocytic and nonphagocytic mammalian cells. Previously, we have described a Listeria monocytogenes-mediated DNA delivery system, which releases plasmid DNA directly into the cytosol of mammalian cells by partial self-destruction of the carrier bacteria. Here we report on a second generation of this phage lysin supported bactofection system, which is greatly improved with respect to plasmid stability, transfer efficacy and biosafety. In this case, DNA release is initiated by spontaneous bacterial lysis in the infected cells cytosol which is subsequently enhanced by the simultaneously released phage lysin produced by the intracellular carrier bacteria. Bacteria that are capable of cell-to-cell spread are found to be much more efficient in bactofection than their non spreading counterparts.

Protein p60 encoded by theiapgene is regarded as an essential gene product ofListeria monocytogenes. Here we report, however, the successful construction of a viableiapdeletion mutant ofL. monocytogenesEGD. The mutant, which produces no p60, shows abnormal septum formation and tends to form short filaments and hooked forms during logarithmic growth. These abnormal bacterial cells break into almost normal sized single bacteria in the late-stationary-growth phase. Theiapmutant is strongly attenuated in a mouse model after intravenous injection, demonstrating the importance of p60 during infection, and the invasiveness of the Δiapmutant for 3T6 fibroblasts and Caco-2 epithelial cells is slightly reduced. Upon uptake by epithelial cells and macrophages, theiapmutant escapes from the phagosome into the cytosol with the same efficiency as the wild-type strain, and the mutant bacteria also grow intracellularly at a rate similar to that of the wild-type strain. Intracellular movement and cell-to-cell spread are drastically reduced in various cell lines, since theiap-negative bacteria fail to induce the formation of actin tails. However, the bacteria are covered with actin filaments. Most intracellular bacteria show a nonpolar and uneven distribution of ActA around the cell, in contrast to that for the wild-type strain, where ActA is concentrated at the old pole. In aniap+revertant strain that produces wild-type levels of p60, intracellular movement, cell-to-cell spread, and polar distribution of ActA are fully restored. In vitro analysis of ActA distribution on the filaments of the Δiapstrain shows that the loss of bacterial septum formation leads to ActA accumulation at the presumed division sites. In the light of data presented here and elswhere, we propose to renameiap(invasion-associated protein)cwhA(cell wall hydrolase A).

The skin and the mucosa of the respiratory and gastrointestinal tracts are continuously exposed to microorganisms, but only a limited number of these enter the body and cause disease. To resist microbial infection, the host has developed a multitude of defense mechanisms involving the innate and adaptive immune systems. Dendritic cells (DCs) provide the link between these arms of the immune system. The initiation of an immune response is critically dependent on the activation of DCs, which can discriminate between different classes of microorganisms and elicit tailored antimicrobial immune responses. They have an extraordinary capacity to stimulate naive T cells and initiate primary immune responses. In turn, some pathogens interfere with DC function to block or delay their elimination by the host. Progress in understanding the role of DCs in the host response to microbes is reviewed.

Dendritic cells (DCs) are major antigen-presenting cells of the immune system, which need to be activated in order to initiate an immune response. Here, we describe the immunostimulatory effects on human monocyte-derived DCs observed upon infection with Listeria monocytogenes or after treatment with listerial lipoteichoic acid (LTA) and lipopolysaccharide (LPS), respectively. All stimuli caused upregulation of costimulatory molecules, induced T-cell proliferative responses and secretion of cytokines in vitro. Infection of DCs with L. monocytogenes induced release of interleukin (IL)-12 and IL-18. In contrast treatment with purified listerial LTA yielded high levels of IL-18 release, but only minimal IL-12 production. Treatment of DCs with LPS conversely induced significant amounts of IL-12 production, but no IL-18. The release of both stimulating cytokines IL-12 and IL-18 upon infection with entire bacteria suggests that attenuated strains of L. monocytogenes may be a valuable tool for subunit vaccine delivery.

Primitive hematopoietic stem cells (HSCs) in the bone marrow are rare pluripotent cells with the capacity to give rise to all lineages of blood cells. During commitment, progenitor cells are composed mainly of cells with the potential for differentiation into 1 or 2 lineages. This commitment involves the acquisition of specific growth factor receptors and the loss of others. Viral and bacterial infections may lead to profound disturbance of hematopoiesis, which is possibly due to different susceptibility of HSCs to infectious agents. Here, we show that quiescent human HSCs are fully resistant to infection by the intracellular bacteria, Listeria monocytogenes andSalmonella enterica serovariationtyphimurium, and the extracellular pathogen Yersinia enterocolitica. During myeloid/monocytic differentiation induced by incubation with stem cell factor, thrombopoietin, and flt-3 ligand, partially differentiated HSCs emerge, which readily take up these pathogens and also latex beads by macropinocytosis. After further monocytic differentiation, bacterial uptake by macropinocytosis still occurs but internalization of the pathogens is now mainly achieved by receptor-mediated phagocytosis. These results suggest that in the case of HSCs uptake mechanisms for bacteria develop sequentially.

Human-monocyte-derived dendritic cells (MoDC) are very efficient in the uptake ofListeria monocytogenes, a gram-positive bacterium which is an important pathogen in humans and animals causing systemic infections with symptoms such as septicemia and meningitis. In this work, we analyzed the influence of blood plasma on the internalization ofL. monocytogenesinto human MoDC and compared the uptake ofL. monocytogeneswith that ofSalmonella entericaserovar Typhimurium andYersinia enterocolitica. While human plasma did not significantly influence the uptake of serovar Typhimurium andY. enterocoliticaby human MoDC, the efficiency of the uptake ofL. monocytogenesby these phagocytes was strongly enhanced by human plasma. In plasma-free medium the internalization ofL. monocytogeneswas very low, whereas the addition of pooled human immunoglobulins resulted in the internalization of these bacteria to a degree comparable to the highly efficient uptake observed with human plasma. All human plasma tested contained antibodies against the 60-kDa extracellular protein ofL. monocytogenes(p60), and anti-p60 antibodies were also found in the commercially available pooled immunoglobulins. Strikingly, in contrast toL. monocytogeneswild type, aniapdeletion mutant (totally deficient in p60) showed only a minor difference in the uptake by human MoDC in the presence or the absence of human plasma. These results support the assumption that antibodies against the listerial p60 protein may play an important role in Fc-receptor-mediated uptake ofL. monocytogenesby human MoDC via opsonization of the bacteria. This process may have a major impact in preventing systemic infection inL. monocytogenesin immunocompetent humans.

Using attenuated intracellular bacteria as carriers, we have developed two different approaches for the delivery of subunit vaccines encoding heterologous antigens. The first system is based on the direct secretion of the heterologous antigens in Gram-negative bacteria via the hemolysin secretion system of Escherichia coli into either phagosome or cytosol of infected cells. The second approach is based on the transport of eukaryotic antigen expression vectors by intracellular bacteria like Listeria and Salmonella into the host cell and here, preferably, into the cytosolic compartment. After release of the plasmid DNA from the bacteria, the plasmid-encoded antigens can be expressed directly by the host cell. Finally, we combined both types of subunit vaccines in one live vector — we equipped Salmonella strains with a phagosomal escape function by utilization of the hemolysin secretion system and used this recombinant vaccine strain for the delivery of a eukaryotic antigen expression vector into the cytosol of macrophages.

Vaccination by intradermal or intramuscular injection of eukaryotic antigen expression vectors (so-called DNA vaccines) elicits strong cellular and humoral immune responses. A novel approach employs attenuated mutant strains of Gram-positive and Gram-negative intracellular bacteria as carriers for the delivery of DNA vaccines. This strategy allows the administration of the DNA vaccines via mucosal surfaces and a direct delivery of the plasmid DNA to professional antigen presenting cells (APC), such as macrophages and dendritic cells (DC). In this work, we have found that several Gram-negative bacteria are capable of delivering plasmid vectors to human DC. In addition, we tested the suitability of the Gram-positive bacterium Listeria monocytogenes as a vaccine carrier for the immunization of fish.

Two different plasmid-vector systems were developed which allow the efficient production and presentation of protein antigens in antigen-presenting cells (APC) by means of virulence-attenuated bacteria. The first antigen-delivery system is based on the secretion machinery of the Escherichia coli hemolysin (HlyA-type I secretion system), which transports proteins, possessing the specific HlyA secretion signal (HlyAs) at the C-terminus, across both membranes of gram-negative bacteria. This system functions in all gram-negative bacteria that possess the TolC-analogous protein in the outer membrane. This outer membrane protein is necessary for the stable anchoring of the type I secretion apparatus in the cell envelope. Suitable HlyAs-fused antigens are secreted with high efficiency by E. coli and by virulence-attenuated strains of Salmonella, Shigella, Vibrio cholerae and Yersinia enterocolitica. The other vector system expresses the heterologous antigen under the control of an eukaryotic promoter in a similar fashion as in plasmids commonly used for vaccination with naked DNA. This plasmid DNA is introduced into APCs with the help of virulence-attenuated self-destructing Listeria monocytogenes mutants. After synthesis of the heterologous protein, epitopes of the antigen are presented by the APC together with MHC class I molecules. This system functions in macrophages and dendritic cells in vitro and can also be used in a modified form in animal models. © 2000 Elsevier Science B.V. All rights reserved.

A key feature of maturation of dendritic cells is the down-regulation of antigen-processing and up-regulation of immunostimulatory capacities. To study the differential expression of transcription factors in this process, we investigated the nuclear translocation and DNA binding of Rel/NF-κB and octamer factors during in vitro generation and maturation of dendritic cells compared with macrophage development. RelB was the only factor strongly up-regulated during the generation of both immature dendritic cells and macrophages. Cytokine-induced maturation of dendritic cells resulted in an increase in nuclear RelB, p50, p52, and especially c-Rel, whereas cytokine-treated macrophages responded poorly. This up-regulation of NF-κB factors did not correlate with lower levels of cytosolic NF-κB inhibitors, the IκBs. One IκB, Bcl-3, was strongly expressed only in mature dendritic cells. Furthermore, generation and maturation of dendritic cells led to a continuous down-regulation of the octamer factor Oct-2, whereas monocytes and macrophages displayed high Oct-2 levels. A similar pattern of maturation-induced changes in transcription factor levels was found in cultured murine epidermal Langerhans cells, suggesting a general physiological significance of these findings. Finally, this pattern of differential activation of Rel and octamer factors appears to be suitable in determining the maturation stage of dendritic cells generated by treatment with different cytokine combinations in vitro. (Blood. 2000;95:277-285)

The data concerning frequency and relevance of the toxin Panton-Valentine leukocidin (PVL) in skin infections caused by Staphylococcus aureus is controversial. The objective of the study was the identification of the role of the toxin in community-acquired skin infections caused by S. aureus.We performed a retrospective analysis of 112 patients with the diagnosis of skin infections caused by S. aureus. Frequency of PVL was investigated by PCR for the lukSF gene. Risk factors and severity of the disease were analyzed. Furthermore, spa typing was done in 55 of the isolated S. aureus.PVL occurred in 45 % of patients with skin infections caused by methicillin-susceptible S. aureus; methicillin-resistant strains were positive in 63 %. Mean age was 30.9 years in PVL-positive infections and thus statistically highly significantly lower than in PVL-negative infections. There was no correlation between presence of PVL and severity and course of skin infections or presence of special risk factors. The spa types showed a high variability in PVL-positive as well as in PVL-negative strains.In our study the PVL status of S. aureus isolated from skin infections was neither correlated with methicillin-resistance nor with the severity of disease. Remarkably, PVL-positive S. aureus strains appeared to be more frequent in younger than in older patients. Our results demonstrate that routine determination of PVL status is not required since the outcome has no diagnostic or therapeutic consequences in daily dermatological practice.

ejd.2013.1981 Auteur(s) : Kristina Buder, Annette Kolb-Maurer Department of Dermatology, Venereology and Allergology, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany; Email: Buder_K@klinik.uni-wuerzburg.de Nail pathologies are important for differential diagnosis of dermatological and systemic diseases. Nail diseases remain an under-represented topic in dermatology. With this issue of the European Journal of Dermatology Residents’ Corner, we open a new section “Nail [...]

We describe a woman presenting primarily with slowly progressing scarring alopecia. Course, symptoms, and clinical picture were highly suggestive for lichen planus. But mycological investigations revealed that cicatricial alopecia was caused by a specific infection with Trichophyton schoenleinii running a chronic course with minimal skin inflammation.