Influence of Thermal Treatment on the Composition of Alpinia officinarum Rhizome.

Alpinia officinarum is a representative of the Zingiberaceae family, which is known for its wide use in the food and pharmaceutical industries also due to its precious pharmacological potential. The major aim of the present study was to evaluate the influence of thermal treatment on the composition of the rhizome of Alpinia officinarum and its antioxidant activity. The fresh rhizome was subjected to various thermal treatment processes-boiling, frying and microwave heating during various time intervals-and their composition and antioxidant activity were determined using chromatographic (HPLC - High Performance Liquid Chromatography and HPLC-MS - High Performance Liquid Chromatography Mass Spectrometry) and spectrophotometric (DPPH and TPC - Total Phenolic Content) methods. Pinobanksin was the main compound found in the extract of the fresh rhizome (537.79 mg/kg), followed by galangin (197.7 mg/kg) and zingerone (185.5 mg/kg). The effect of thermal treatment on the rhizome composition was varied. In general, thermal processing significantly decreased the content of active compounds in the rhizome. However, there were some exceptions-boiling for 4 min significantly increased the content of pinobanksin (1162.4 mg/kg) and galangin (280.7 mg/kg), and microwave processing for 4 min increased the content of pinocembrin (213 mg/kg). It was found that boiling and microwave treatment significantly increased the antioxidant activity of the processed rhizomes.

The Intersection of Human and Veterinary Medicine-A Possible Direction towards the Improvement of Cell Therapy Protocols in the Treatment of Perianal Fistulas.

The effective treatment of perianal fistulizing Crohn's disease is still a challenge. Local administration of mesenchymal stromal cells (MSCs) is becoming a part of accepted treatment options. However, as a fledgling technique, it still can be optimized. A new trend in translational research, which is in line with "One Health" approach, bases on exploiting parallels between naturally occurring diseases affecting humans and companion animals. Canine anal furunculosis (AF) has been indicated as condition analogous to human perianal Crohn's disease (pCD). This narrative review provides the first comprehensive comparative analysis of these two diseases based on the published data. The paper also outlines the molecular mechanisms of action of MSCs which are likely to have a role in modulating the perianal fistula niche in humans, and refers them to the current knowledge on the immunomodulatory properties of canine MSCs. Generally, the pathogenesis of both diseases shares main determinants such as the presence of genetic predispositions, dysregulation of immune response and the relation to intestine microbiota. However, we also identified many aspects which should be further specified, such as determining the frequency of true fistulas formation in AF patients, elucidating the role of TNF and Th17 pathway in the pathogenesis of AF, or clarifying the role of epithelial-to-mesenchymal transition phenomenon in the formation of canine fistulae. Nevertheless, the available data support the hypothesis that the results from testing cell therapies in dogs with anal furunculosis have a significant translational value in optimizing MSC transplants procedures in pCD patients.

Comportamiento de la IgE y las subclases de IgG en las infecciones por Staphylococcus aureus / Manifestation of IgE and IgG subclasses in Staphylococcus aureus infections

RESUMEN Introducción: Las infecciones cutáneas por Staphylococcus aureus, se presentan con alta frecuencia en la comunidad. La forma superficial de esta es la foliculitis. Una extensión hacia el tejido subcutáneo da como resultado la formación de una lesión supurativa local llamada forúnculo. Aproximadamente el 20 % de los pacientes con forúnculo presentan una o más recidivas durante el año siguiente, y cierto número presenta forunculosis recidivante crónica durante meses o años. Objetivo: Conocer el comportamiento de los niveles de IgE y las subclases de IgG expresadas en pacientes y controles, para inferir el patrón de la respuesta inmune a la infección. Métodos: Se realizó un estudio prospectivo donde se determinaron las subclases de inmunoglobulina G (IgG) y los niveles de inmunoglobulina E (IgE) en suero de 25 enfermos con lesiones cutáneas por Staphylococcus aureus, y 25 controles sanos, provenientes del banco de sangre. Se elaboró un antígeno (Bacterina de Staphylococcus aureus) y en su enfrentamiento se procedió con la metodología de normalización y validación de ensayos inmunoenzimáticos para cuantificar IgG humana. Los resultados se expresaron en densidades ópticas y gráficamente como la relación matemática (IgG1/3) para Th1 e (IgE/IgG4) para Th2, en el suero de los pacientes. Resultados: Se obtuvo respuesta IgG1 e IgG4 en pacientes y controles y respuesta IgE anti Staphylococcus aureus en pacientes. Conclusiones: Como Staphylococcus aureus es flora normal de la piel, los controles ya han tenido contacto con él, lo que provoca el desarrollo de respuesta Th1 (IgG1) y anticuerpos bloqueadores (IgG4). Contrariamente, los enfermos desarrollan respuesta Th2 (IgE) y la infección.

ABSTRACT Introduction: Staphylococcus aureus skin infections occur with high frequency in the community. Folliculitis is its superficial form. An extension into the subcutaneous tissue results in the formation of a local suppurative lesion known as a furunculosis. Approximately 20% of patients with a furuncle have one or more recurrences over the next year, and a certain number have chronic relapsing furunculosis for months or years. Objective: to know the manifestation of IgE levels and IgG subclasses expressed in patients and controls, to infer the pattern of the immune response to infection. Methods: we conducted a prospective study where immunoglobulin G (IgG) subclasses and immunoglobulin E (IgE) levels were determined in serum of 25 ill patients with Staphylococcus aureus skin lesions, and 25 healthy controls, from the blood bank. An antigen (Staphylococcus aureus bacterin) was elaborated and in its confrontation, the normalization and validation methodology of immunoenzymatic assays to quantify human IgG was carried out. The results were expressed in optical densities and graphically as the mathematical ratio (IgG1/3) for Th1 and (IgE/IgG4) for Th2, in the serum of the patients. Results: IgG1 and IgG4 responses were obtained in patients and controls, and anti-Staphylococcus aureus IgE responses in patients. Conclusions: the controls have already had contact with Staphylococcus aureus, as it is normal flora of the skin, which causes the development of Th1 response (IgG1) and antibodies blockers (IgG4). On the contrary, ill patients develop a Th2 response (IgE) and the infection.

A Bioactive Extract Rich in Triterpenic Acid and Polyphenols from Olea europaea Promotes Systemic Immunity and Protects Atlantic Salmon Smolts Against Furunculosis.

In the present study, the modulation of the transcriptional immune response (microarray analysis) in the head kidney (HK) of the anadromous fish Atlantic salmon (Salmo salar) fed a diet supplemented with an olive fruit extract (AQUOLIVE®) was evaluated. At the end of the trial (133 days), in order to investigate the immunomodulatory properties of the phytogenic tested against a bacterial infection, an in vivo challenge with Aeromonas salmonicida was performed. A total number of 1,027 differentially expressed genes (DEGs) (805 up- and 222 downregulated) were found when comparing the transcriptomic profiling of the HK from fish fed the control and AQUOLIVE® diets. The HK transcripteractome revealed an expression profile that mainly favored biological processes related to immunity. Particularly, the signaling of i-kappa B kinase/NF-kappa and the activation of leukocytes, such as granulocytes and neutrophils degranulation, were suggested to be the primary actors of the innate immune response promoted by the tested functional feed additive in the HK. Moreover, the bacterial challenge with A. salmonicida that lasted 12 days showed that the cumulative survival was higher in fish fed the AQUOLIVE® diet (96.9 ± 6.4%) than the control group (60.7 ± 13.5%). These results indicate that the dietary supplementation of AQUOLIVE® at the level of 0.15% enhanced the systemic immune response and reduced the A. salmonicida cumulative mortality in Atlantic salmon smolts.

Proteinograma e inmunoglobulinas séricas en las infecciones cutáneas por Staphylococcus aureus / Proteinogram and serum immunoglobulins in skin infections caused by Staphylococcus aureus

RESUMEN Introducción: lesión típica ocasionada por el Staphylococcus aureus es el furúnculo o cualquier otro absceso localizado. Objetivo: describir el comportamiento del proteinograma y los niveles de inmunoglobulinas séricas. Métodos: se realizó un estudio longitudinal prospectivo con 70 pacientes portadores de forúnculos infectados por Staphylococcus aureus, que acudieron a las consultas de Inmunología en varias localidades de Villa Clara. Resultados: se determinaron las fracciones proteicas por método de elusión; se cuantificaron las inmunoglobulinas séricas por inmunodifusión radial simple, según edad, sexo y color de la piel de los pacientes. Se contrastaron las variables bajo la prueba de Ji cuadrado, con una significación de confianza del 95 %. Predominaron los pacientes con el color de la piel blanca sobre los no blancos. En la electroforesis de proteínas se obtuvieron resultados normales para las proteínas totales y la fracción gamma. Para la albúmina, fracción alfa 1, alfa 2 y beta globulina se obtuvieron valores bajos, por encima del 95 % válido. Conclusiones: todas las inmunoglobulinas resultaron normales o altas, según los intervalos de referencia para cada grupo de edad. Al correlacionar los valores de las inmunoglobulinas con las fracciones de la electroforesis, fue llamativo el resultado obtenido en la correlación entre la IgA y la fracción beta. De manera general, los anticuerpos no mostraron variaciones significativas en sus correlaciones, lo cual evidenció un pobre papel en la infección. Se concluyó que los valores de alfa 1, alfa 2 y beta globulina pueden tener importancia en la enfermedad.

ABSTRACT Introduction: the typical lesion caused by Staphylococcus aureus is the furuncle or any other localized abscess. Objective: to describe the manifestation of the proteinogram and serum immunoglobulin levels. Methods: a prospective longitudinal study was carried out in 70 patients with furuncles infected by Staphylococcus aureus, who came to the Immunology consultations from various locations of Villa Clara. Results: protein fractions were determined by elution method; serum immunoglobulins were quantified according to age, gender and skin color of the patients by simple radial immunodiffusion. Variables were contrasted under the Chi-square test, with 95% confidence significance. White patients predominated over non-white ones. Normal results were obtained for total proteins and gamma fraction in protein electrophoresis. Low values were obtained for albumin, alpha 1, alpha 2 and beta globulin fraction, above 95% valid. Conclusions: all immunoglobulins were normal or high, according to the reference intervals for each age group. The result obtained in the correlation between IgA and the beta fraction was striking when correlating the immunoglobulin values with the electrophoresis fractions. In general, the antibodies did not show significant variations in their correlations, which evidenced a poor role in infection. We concluded that alpha 1, alpha 2 and beta globulin values may be important in the disease.

Mammary Hidradenitis Suppurativa Lesions - A Suggestion for Phenotyping.

BACKGROUND: Hidradenitis suppurativa (HS) is an under-diagnosed chronic inflammatory skin disease of the pilosebaceous unit of apocrine gland-rich parts of the body. The mammary area is the fourth most HS-affected area and, as typical lesions include non-fluctuating nodules, abscesses, and tunnels/sinus tracts, mammary HS is often mistaken for other mammary "boils", such as sub-areolar and granulomatous non-lactating breast abscesses. Our objective was to present a spectrum of mammary HS lesions, explore a possible classification, and expose mammary HS as a possible differential diagnosis to non-lactational breast abscesses. METHODS: A cross-sectional study on current and newly-referred patients treated for HS affecting the mammary area. Anamnestic information, subjective outcome measures, and lesion counts including anatomical location were collected. Patients with similar morphologies were grouped, and characteristics for the groups were investigated. LIMITATIONS: We were not aware of the number of morphologies we would find, and as a result the study did not have sufficient power to show significant differences after correction for multiple testing. RESULTS: We found three morphologically different subtypes of mammary HS; the Sternal, the Frictional, and the Nodule types. These groups differed in anatomical lesion characteristics and other patient characteristics. Furthermore, we found a fourth Mixed type - a combination of the other three. CONCLUSION: Differential diagnosis between mammary HS and sub-areolar or granulomatous non-fluctuating non-lactating breast abscess is most easily performed by assessing the precise anatomical location of the lesion and determining if the mammary lesion is the only lesion present or if similar lesions exist in other HS-specific areas.

GAS1: A New ß-Glucan Immunostimulant Candidate to Increase Rainbow Trout (Oncorhynchus mykiss) Resistance to Bacterial Infections With Aeromonas salmonicida achromogenes.

ß-glucans are prebiotic and/or food additives used by the aquaculture industry to enhance the immune response of fish. Their efficiency may vary according to their origin and structure. In this study, the immunostimulant effects of two ß-glucan types extracted from wild-type baker's yeast (Saccharomyces cerevisiae) and its null-mutant Gas1 were investigated. Gas1 has a beta-1,3-glucanosyltransferase activity necessary for cell wall assembly. Using a positive (commercial product MacroGard®) and a negative control (a diet without glucans), we evaluated the immune responses and disease resistance of rainbow trout juveniles (mean weight, ~44 g) fed control, low (0.2%) and high (0.5%) doses of Macrogard®, Gas1, and Wild type-ß-glucan after a short-term (15 days, D15) or mid-term (36 days, D36) feeding periods. We found that ß-glucan supplemented diets did not affect growth performance, mortality, splenic index, or leukocyte respiratory burst activity on D15 nor D36. However, each ß-glucan triggered different immune effectors, depending of the doses or length of exposure compared to others and/or the negative control. Indeed, high dose of MacroGard® significantly increased lysozyme activities at D15 compared with the control and other diets (p<0.05). At D36, MacroGard ß-glucan enhanced the production of lymphocytes in comparison with the control diet (p<0.05). Regarding WT ß-glucan, at D36, WT-ß-glucan, especially the high dose, provided the highest enzymatic activities (lysozyme and ACH50) and Ig level (p<0.01). Furthermore, on D36, Gas1 also increased lysozyme activity, Ig proportion, and some immune genes (mcsfra, hepcidin) compared with MacroGard® (p<0.05). Besides, both doses of Gas1-ß-glucans increased the resistance of juveniles to bacterial infection highlighted by a higher survival rate at 14 days post-challenge compared with the control and other types and doses of ß-glucans (p<0.05). In conclusion, our results suggest that Gas1-ß-glucan could represent a promising immunostimulant that would help to prevent diseases in aquaculture even more efficiently than other ß-glucans already in use. Mode of action and particular efficiency of this new Gas1 mutant are debated.

Metastatic endophthalmitis presenting as subretinal abscess following a forearm furuncle.

Metastatic endophthalmitis (ME) is rare form of secondary uveitis commonly prevalent in immunocompromised patients. A 55-year-old immunocompetent woman presented with painful decrease in left eye vision (referred to us as cytomegalovirus retinochoroiditis). Ocular examination revealed diffuse yellowish-white retinitis lesion (diagnosed as subretinal abscess on macular optical coherence tomography). Vitreous tap was unremarkable, but vitreous biopsy from the posterior vitreous overlying the subretinal abscess confirmed the growth of methicillin-sensitive Staphylococcus aureus (MSSA). Detailed systemic examination revealed a forearm furuncle, which yielded MSSA on culture. The infection followed relentless course despite aggressive treatment with pars plana vitrectomy and antibiotics (topical, systemic and intravitreal). This case is presented due to rarity of presentation of ME as subretinal abscess following skin infection, which became a management challenge. Due to its rapid progression and irreversible damage to ocular tissue, high index of suspicion and aggressive management is needed in such cases. The disease course, management and prognosis of such cases are dismal in majority of the patients.

Novel atypical Aeromonas salmonicida bath challenge model for juvenile ballan wrasse (Labrus bergylta, Ascanius).

Atypical Aeromonas salmonicida (aAs) is currently one of the most routinely recovered bacterial pathogens isolated during disease outbreaks in farmed cleaner fish, ballan wrasse (Labrus bergylta, Ascanius). Vibrionaceae family bacteria have also been isolated from ballan wrasse in Scotland. This study determined the infectivity, pathogenicity and virulence of aAs and Vibrionaceae isolates in juvenile farmed ballan wrasse (n = 50; approx. 2 g) using a bath challenge, and fish were monitored for a period of 16 days. Atypical As caused significant mortalities in contrast to Vibrionaceae isolates. Notably, differential virulence was observed between two aAs vapA type V strains at similar challenge doses. Diseased fish exhibited a systemic infection where aAs was detected in all analysed tissues (liver, spleen and kidney) by PCR and qPCR. Macroscopically, moribund and survivor fish exhibited hepatomegaly and splenomegaly. In moribund and surviving fish, histopathology showed granulomatous hepatitis with eosinophilic granular cells surrounding bacterial colonies and endocarditis along with splenic histiocytosis. This is the first report of a successful aAs bath challenge model for juvenile ballan wrasse which provides an important tool for future studies on vaccine efficacy and immunocompetence.

Pathogenic characterization of Aeromonas salmonicida subsp. masoucida turbot isolate from China.

Aeromonas salmonicida is a gram-negative bacterium that is the causative agent of furunculosis. An A. salmonicida strain was isolated from diseased turbot (Scophthalmus maximus) with the sign of furunculosis from North China. Based on vapA gene, the strain was further classified as A. salmonicida subsp. masoucida RZ6S-1. Culturing RZ6S-1 strain at high temperature (28°C) obtained the virulence attenuated strain RZ6S. Genome sequence comparison between the two strains revealed the loss of the type IV secretion system (T4SS) and type III secretion system (T3SS) from the native plasmid pAsmB-1 and pAsmC-1 of wild-type strain RZ6S-1, respectively. Further study demonstrated that the wild-type strain RZ6S-1, but not its derivative mutant RZ6S, can stimulate apoptosis. Elevated protein level of cleaved caspase-3 was detected from epithelioma papulosum cyprinid (EPC) cells infected with wild-type strain RZ6S-1 as compared with that infected with RZ6S strain. Meanwhile, the invasion of the mutant strain RZ6S was about 17-fold higher than the wild-type strain RZ6S-1, suggesting that some protein(s) from A. salmonicida subsp. masoucida RZ6S-1 suppress its invasion. The RZ6S mutant strain was attenuated, since its LD50 is over 10,000 times higher compared to the wild-type strain as revealed in the turbot infection model.

Dysbiosis in a canine model of human fistulizing Crohn's disease.

Crohn's disease (CD) is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance toward the commensal microbiota. On average, 29.5% and 42.7% CD patients experience perianal complications at 10 and 20 y after diagnosis, respectively. Perianal CD (pCD) result in high disease burden, diminished quality of life, and elevated health-care costs. Overall pCD are predictors of poor long-term outcomes. Animal models of gut inflammation have failed to fully recapitulate the human manifestations of fistulizing CD. Here, we evaluated dogs with spontaneous canine anal furunculosis (CAF), a disease with clinical similarities to pCD, as a surrogate model for understanding the microbial contribution of human pCD pathophysiology. By comparing the gut microbiomes between dogs suffering from CAF (CAF dogs) and healthy dogs, we show CAF-dog microbiomes are either very dissimilar (dysbiotic) or similar (healthy-like), yet unique, to healthy dog's microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance of Bacteroides vulgatus and Escherichia coli and a decreased abundance of Megamonas species and Prevotella copri. Our results mirror what have been reported in previous microbiome studies of patients with CD; particularly, CAF dogs exhibited two distinct microbiome composition: dysbiotic and healthy-like, with determinant bacterial taxa such as E. coli and P. copri that overlap what it has been found on their human counterpart. Thus, our results support the use of CAF dogs as a surrogate model to advance our understanding of microbial dynamics in pCD.

Severe pediculosis capitis in a nursery school girl / Pediculosis capitis grave en una niña inscrita en una guardería

Pediculosis capitis is the most frequent ectoparasitosis around the world. The infestation is caused by Pediculus humanus capitis (head louse), which affects hair, scalp, and skin. It rarely presents with more symptoms and in the majority of the cases, it shows a benign course if treated properly. We present the case of a nursery school girl with head lice infestation for 18 months. She did not improve after the shampoo treatment. This case was associated with furunculosis, skin lesions, multiple adenopathies, and anemia. Initially, the presence of boils, alopecia, and lymphadenopathy was evident. The persistence of pediculosis capitis and intense scratching induced changes on skin integrity, facilitating opportunistic bacterial superinfection that led to impetiginization, furunculosis, excoriations, hematic scabs, anemia, alopecia, and lymphadenopathies. Pediculosis capitis affected the patient triggering psychological, economic, social, and other health problems. The patient presented uncommon symptoms (furunculosis, anemia, fever, alopecia, and adenopathies) resulting from the persistence of risk factors and the absence of head inspection and mechanical removal of insects. The education about the risk factors, as well as sanitary controls, are essential to contain the infestation.

La pediculosis capitis es la ectoparasitosis más frecuente a nivel mundial. La infestación es causada por Pediculus humanus capitis (piojo de la cabeza) y afecta el cabello, el cuero cabelludo y la piel. Rara vez se manifiesta con otro tipo de sintomatología y, por lo general, su curso es benigno si se trata adecuadamente. Se presenta el caso de una menor con pediculosis capitis de 18 meses de evolución, asociada con forúnculos, lesiones cutáneas, múltiples adenopatías y anemia, que no mejoró tras la aplicación del champú. Inicialmente, llamó la atención la presencia de forúnculos, alopecia y adenopatías. La persistencia de la pediculosis capitis y el rascado intenso alteraron la integridad de la epidermis y facilitaron las infecciones secundarias por bacterias patógenas y oportunistas que produjeron impétigo, forunculosis, excoriaciones, costras hemáticas, anemia, alopecia y linfadenopatías. La pediculosis capitis afectó notoriamente a la paciente al causarle problemas psicológicos y de salud, agudizados por su condición económica y social. La paciente presentó manifestaciones clínicas poco frecuentes (forunculosis, anemia, fiebre, alopecia y adenopatías), lo cual se vio facilitado por la persistencia de los factores de riesgo y el hecho de que no se le inspeccionaba la cabeza ni se removían los insectos. La educación sobre los factores de riesgo y el control sanitario es indispensable para controlar la infestación.

Pediculosis capitis grave en una niña inscrita en una guardería / Severe pediculosis capitis in a nursery school girl

La pediculosis capitis es la ectoparasitosis más frecuente a nivel mundial. La infestación es causada por Pediculus humanus capitis (piojo de la cabeza) y afecta el cabello, el cuero cabelludo y la piel. Rara vez se manifiesta con otro tipo de sintomatología y, por lo general, su curso es benigno si se trata adecuadamente. Se presenta el caso de una menor con pediculosis capitis de 18 meses de evolución, asociada con forúnculos, lesiones cutáneas, múltiples adenopatías y anemia, que no mejoró tras la aplicación del champú. Inicialmente, llamó la atención la presencia de forúnculos, alopecia y adenopatías. La persistencia de la pediculosis capitis y el rascado intenso alteraron la integridad de la epidermis y facilitaron las infecciones secundarias por bacterias patógenas y oportunistas que produjeron impétigo, forunculosis, excoriaciones, costras hemáticas, anemia, alopecia y linfadenopatías. La pediculosis capitis afectó notoriamente a la paciente al causarle problemas psicológicos y de salud, agudizados por su condición económica y social. La paciente presentó manifestaciones clínicas poco frecuentes (forunculosis, anemia, fiebre, alopecia y adenopatías), lo cual se vio facilitado por la persistencia de los factores de riesgo y el hecho de que no se le inspeccionaba la cabeza ni se removían los insectos. La educación sobre los factores de riesgo y el control sanitario es indispensable para controlar la infestación.

Pediculosis capitis is the most frequent ectoparasitosis around the world. The infestation is caused by Pediculus humanus capitis (head louse), which affects hair, scalp, and skin. It rarely presents with more symptoms and in the majority of the cases, it shows a benign course if treated properly. We present the case of a nursery school girl with head lice infestation for 18 months. She did not improve after the shampoo treatment. This case was associated with furunculosis, skin lesions, multiple adenopathies, and anemia. Initially, the presence of boils, alopecia, and lymphadenopathy was evident. The persistence of pediculosis capitis and intense scratching induced changes on skin integrity, facilitating opportunistic bacterial superinfection that led to impetiginization, furunculosis, excoriations, hematic scabs, anemia, alopecia, and lymphadenopathies. Pediculosis capitis affected the patient triggering psychological, economic, social, and other health problems. The patient presented uncommon symptoms (furunculosis, anemia, fever, alopecia, and adenopathies) resulting from the persistence of risk factors and the absence of head inspection and mechanical removal of insects. The education about the risk factors, as well as sanitary controls, are essential to contain the infestation.

Systemic infection in European perch with thermoadapted virulent Aeromonas salmonicida (Perca fluviatilis).

In non-salmonid fish, Aeromonas salmonicidacan cause local infections with severe skin ulcerations, known as atypical furunculosis. In this study, we present a systemic infection by a virulent A. salmonicidain European perch (Perca fluviatilis).This infection was diagnosed in a Swiss warm water recirculation aquaculture system. The isolate of A.  salmonicida encodes a type three secretion system (TTSS) most likely located on a plasmid similar to pAsa5/pASvirA, which is known to specify one of the main virulence attributes of the species A. salmonicida. However, the genes specifying the TTSS of the perch isolate show a higher temperature tolerance than strains isolated from cold-water fish. The function of the TTSS in virulence was verified in a cytotoxicity test using bluegill fry and epithelioma papulosum cyprinid cells.

TNF overproduction impairs epithelial staphylococcal response in hyper IgE syndrome.

Autosomal dominant hyper IgE syndrome (AD-HIES), or Job's syndrome, is a primary immune deficiency caused by dominant-negative mutations in STAT3. Recurrent Staphylococcus aureus skin abscesses are a defining feature of this syndrome. A widely held hypothesis that defects in peripheral Th17 differentiation confer this susceptibility has never been directly evaluated. To assess the cutaneous immune response in AD-HIES, we induced suction blisters in healthy volunteers (HVs) and patients with AD-HIES and then challenged the wound with lethally irradiated bacteria. We show that cutaneous production of IL-17A and IL-17F was normal in patients with AD-HIES. Overproduction of TNF-α differentiated the responses in AD-HIES from HVs. This was associated with reduced IL-10 family signaling in blister-infiltrating cells and defective epithelial cell function. Mouse models of AD-HIES recapitulated these aberrant epithelial responses to S. aureus and involved defective epithelial-to-mesenchymal transition (EMT) rather than a failure of bacterial killing. Defective responses in mouse models of AD-HIES and primary keratinocyte cultures from patients with AD-HIES could be reversed by TNF-α blockade and by drugs with reported modulatory effects on EMT. Our results identify these as potential therapeutic approaches in patients with AD-HIES suffering S. aureus infections.

Phenotype of Aeromonas salmonicida sp. salmonicida cyclic adenosine 3',5'-monophosphate receptor protein (Crp) mutants and its virulence in rainbow trout (Oncorhynchus mykiss).

Precise deletion of genes related to virulence can be used as a strategy to produce attenuated bacterial vaccines. Here, we study the deletion of the cyclic-3',5'-adenosine monophosphate (cAMP) receptor protein (Crp) in Aeromonas salmonicida, the aetiologic agent of furunculosis in marine and freshwater fish. The Crp protein is a conserved global regulator, controlling physiology processes, like sugar utilization. Deletion of the crp gene has been utilized in live attenuated vaccines for mammals, birds and warm water fish. Here, we characterized the crp gene and reported the effect of a crp deletion in A. salmonicida virulent and non-virulent isolates. We found that A. salmonicida Δcrp was not able to utilize maltose and other sugars, and its generation time was similar to the wild type. A. salmonicida ∆crp showed a higher ability of cell invasion compared to the wild type. Fish challenges showed that A. salmonicida ∆crp is ~6 times attenuated in Oncorhynchus mykiss and conferred protective immunity against the intraperitoneal challenge with A. salmonicida wild type. We concluded that deletion of A. salmonicida crp influences sugar utilization, cell invasion and virulence. Deletion of crp in A. salmonicida could be considered as part of an effective strategy to develop immersion live attenuated vaccines against furunculosis.