In Situ Immune Response in Human Chromoblastomycosis – A Possible Role for Regulatory and Th17 T Cells

Background

Chromoblastomycosis is a chronic fungal infection that affects skin and subcutaneous tissue. Lesions can be classified in tumorous, verrucous, cicatricial and plaque type. The cellular immune response in the severe form of the disease seems to correlate with a Th2 pattern of cytokines. The humoral immune response also seems to play a role. We intended to explore the populations of regulatory T cells and the Th17 pattern.

Methodology

Twenty-three biopsies of verrucous form were obtained from patients with clinical, culture and histopathological diagnostic of chromoblastomycosis, without treatment. It was performed an immunohistochemistry method to detect Foxp3, CD25, TGF-β, IL-6, IL-17 and IL-23.

Principal findings

IL-17 was the only cytokine with high expression in CBM when compared to normal skin. The expression of Treg cells, TGF- β, IL-6 and IL-23 were similar to normal skin.

Conclusions/Significance

The constitution of a local immune response with high expression of IL-17 and low expression of other cytokines could be at least in part, an attempt to help the immune system against fungal infection. On the other hand, high levels of local immune response mediated by Th17 profile could overcome the role of Treg cells. The inefficient immunomodulation as a consequence of the unbalance by Treg/Th17 cells seems to corroborate with the less effective immune response against fungi.     

A study of reproductive females of the freshwater crayfish Austropotamobius pallipes

Details of the female annual reproductive cycle in the population from Northumberland are given. Mating occurs in October and is followed by egg laying in early November. Eggs are carried by females until the following July–August when hatching occurs. The smallest berried female caught was 25 mm carapace length (C.L.) and this was chosen as the minimum size for adult females. Only 40–50% of adult females, hand-caught, were berried in the Spring following egg laying; but this percentage was low largely because few females in the size classes below 28 mm C.L. were berried. The reasons for adult females being non-reproductive in a year are discussed.     

Pericentromeric structure of human X “isochromosomes”: evidence for molecular heterogeneity

Summary Three different long-arm X isochromosomes and an isodicentric X chromosome were examined by in situ hybridization with X-chromosome-specific -satellite probes and by quantitation of Southern blots hybridized with proximal short-arm probes. Each chromosome had a unique pericentromeric structure. The isodicentric X chromosome was clearly dicentric, showing two distinct -satellite hybridization signals and duplication of short-arm material. Two isochromosomes showed a larger than normal, bifid -satellite signal and also had duplications of different extents of short-arm material. The third X isochromosome could not be distinguished from a classical long-arm isochromosome; it did not have a short-arm duplication and it had a single -satellite signal. These data indicate that rearrangements responsible for X isochromosome formation can occur at numerous locations in the pericentromeric region and that some X isochromosomes may involve duplications of substantial portions of the short arm.     

A Case Report of Widespread Majocchi’s Granuloma in a Patient with Systemic Lupus Erythematosus

Majocchi’s granuloma is an intracutaneous or subcutaneous granulomatous inflammation caused by invasion of dermatophytic fungus, especially Trichophyton rubrum. This type of lesion is misdiagnosed frequently without proper auxiliary examination. Here, we report a case of widespread Majocchi’s granuloma caused by T. rubrum in a 35-year-old woman with systemic lupus erythematosus for 9 years. The patient was initially misdiagnosed as SLE-associated skin lesions, which delayed her treatment and resulted in severe multiple disseminated lesions. After confirmed as Majocchi’s granuloma, the patient was cured after 11-month treatment with terbinafine.     

Polymorphism of the Interleukin- and Interleukin Receptor Genes: Population Distribution and Association with Atopic Asthma

Population distribution and pathogenetic significance for bronchial asthma (BA) of the eight polymorphic variants of six interleukin- (IL) and interleukin receptor genes, C-589T, G/C 3"-UTRIL4, C-703T IL5 T113M IL9 Q551R, 150V IL4RA, G-80A IL5RA, and G1972A IL5RB, was examined. In the population samples of Russians, Tajiks, Buryats, and Tuvinians racial and ethnic specificity of these polymorphisms was established. These specific features were manifested as population-specific genetic portraits in respect of polymorphic allele frequencies. Analysis of the BA patients and their relatives from Tomsk by use of transmission/disequilibrium test (TDT) revealed the presence of a statistically significant association between the C-703 IL5 allele and the disease (P= 0.005). This is the first evidence of an association between the IL5 gene polymorphism and BA.     

Coccidioidomycosis and other endemic mycoses in Mexico

The endemic mycoses traditionally include coccidioidomycosis, histoplasmosis, blastomycosis and paracoccidioidomycosis. Although sporotrichosis and chromomycosis are technically not included among the endemic mycoses, they are frequently diagnosed in Mexico. Most systemic endemic mycoses are a consequence of inhaling the fungi, while subcutaneous mycoses are acquired through the inoculation of vegetable matter or soil containing the organism. Coccidioidomycosis is caused by Coccidioides spp., a dimorphic pathogenic fungus. Approximately 60% of exposures result in asymptomatic infection; in the rest there are protean manifestations that range from a benign syndrome also known as "Valley Fever" to progressive pulmonary or extrapulmonary disease. Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic to the Americas. Pulmonary histoplasmosis manifestations are protean, ranging from a brief period of malaise to a severe, prolonged illness. The spectrum of illness in disseminated histoplasmosis ranges from a chronic, intermittent course to an acute and rapidly fatal infection. Paracoccidioidomycosis is a chronic, granulomatous systemic disease caused by Paracoccidioides brasiliensis that characteristically produces a primary pulmonary infection, often asymptomatic, and then disseminates to form ulcerative granulomata of the oral, nasal and occasionally the gastrointestinal mucosa. Sporotrichosis, caused by Sporothrix schenckii, has diverse clinical manifestations; the most frequent is the lymphocutaneous form. Generally, infection results from inoculation of the fungus through thorns, splinters, scratches and small traumas. Chromomycosis (Chromoblastomycosis) is a slowly progressive cutaneous and subcutaneous mycosis attributed to various saprophyte Hypomycetes fungi. The primary lesion is also thought to develop as a result of percutaneous traumatic inoculation.     

Screening for Ergot Alkaloid Producers among Microscopic Fungi by Means of the Polymerase Chain Reaction

The potential of the polymerase chain reaction for the detection of ergot alkaloid producers among microscopic fungi of the generaPenicilliumand Clavicepswas evaluated. Twenty-three strains of various species of fungi with a previously studied capacity for alkaloid production were used. The internal fragment of the gene encoding 4-dimethylallyltryptophan synthase, the enzyme catalyzing the first step in the biosynthesis of ergot alkaloids, was amplified using degenerate primers. This approach revealed an about 1.2-kb specific DNA fragment in micromycetes synthesizing ergot alkaloids with complete tetracyclic ergoline system. Microorganisms that produce alkaloids with modified C or D ergoline rings, as well as -cyclopiazonic acid, did not yield the PCR fragment of the expected size. This fragment was also not found in fungi incapable of ergot alkaloid production.     

Cutaneous silica granuloma

Cutaneous silica granuloma is a rare and fascinating cause of delayed scarring. Symptoms may arise many years after minor wounding if glass, sand, or other silica-containing particles have been embedded. Such granulomatous lesions are often nodular, indurated, and erythematous. They may respond to surgical excision or medical treatment, and in rare cases, they may spontaneously regress. We present one case in which three separate areas of cutaneous silica granulomas developed after a latent period of about 20 years and then involuted without intervention. The etiology and therapeutic options are discussed.     

The effects of ductal ligation on the parenchyma of salivary glands of cat studied by enzyme histochemical methods

Synopsis Submandibular, sublingual and parotid glands of cat have been studied following periods of ductal ligation ranging from 1 day to 1 year. An increased prominence of granules of acid phosphatase, -glucuronidase and E600-resistant esterase reaction products was sometimes seen in acinar cells and atrophic striated ductal cells, and probably represents increased lysosomal enzymic activity, which may be of importance in the adaptation of the parenchyma to the altered environment. Other reaction products often appeared to be at normal levels in parenchymal structures that were not very atrophic, and at reduced levels in those that were very atrophic, suggesting a reduction of functional activity in these structures.     

Determination of Β-isomerized aspartic acid as the corresponding alcohol

The age-related formation of succinimides in proteins, through spontaneous deamidation of asparagine, and through cyclization of aspartic acid, is thought to be followed by the hydrolysis of the succinimide ring, yielding a mixture of normal aspartic acid sites and-isomerized aspartic acid sites (isoaspartic acid). The chemical reduction of an isoaspartyl site to the corresponding amino acid alcohol, isohomoserine, has now been investigated as a general approach to measuring the accumulation of isomerized residues in aging proteins. The methods employed were based on conditions previously found to be successful in reducing protein aspartic acid to homoserine. Borane was employed as the reducing agent, and was found to produce the expected amino acid alcohols in reactions with model peptides. In addition, amino acid analysis revealed a complex pattern of unknown products of these reduction reactions, some of which were also evident when a much stronger reducing agent, lithium aluminum hydride, was used. The correlation of some of these side-products with the isomerization of the peptide suggests, unexpectedly, that the reactivity of reducing agents toward aspartyl residues and perhaps other sites in the peptide may be influenced by steric factors related to aspartyl isomerization. The borane reduction method was also applied to proteins. No detectable isohomoserine was formed either in ovalbumin, a model aged protein, or in human lens proteins of advanced age, with conditions that fully reduced normal aspartyl residues to homoserine. These tests thus indicate that the percentage of aspartic acid in the isomerized form in these proteins is below the limit of detectability (below 5%). These results complement previous experimental results that have indicated a low bulk isoaspartyl content in most natural proteins.     

Pathology of the human pulmonary paracoccidioidomycosis

Lungs of twelve patients with chronic paracoccidioidomycosis (Pb) were studied in an attempt to understand the pathogenesis of the pulmonary disease. Ribbons of the lung parenchyma including the hilar region and directed towards apical, basal and lateral regions were subdivided into sections from the hilar, intermediate and peripheral segments. The following histopathological reactions directly or indirectly related to P. brasiliensis were described and analysed in relation to the number of slides studied and the pulmonary region involved: (1) pneumonic reaction; (2) early granulomatous formation; (3) mature and healed granulomata; (4) mixed pattern (early and mature granuloma in the same pulmonary area visualized in the slide); (5) pulmonary fibrosis.It was concluded that chronic pulmonary Pb is a recurrent disease affecting equally both lungs. Fibrosis was connected mainly with the progressive evolution of the granulomata towards cicatrization and to a lesser degree probably to a direct induction by the fungi. Based chiefly on the tendency of the fibrosis to run around bronchi and to make up septa interconnecting bronchi and vessels it was hipothesized that these findings were the result of a previous chronic specific lymphangitis by the fungi. Hilar fibrosis would be the result of this lymphangitis and/or of the progression of the specific granulomatous reaction seen in the hilar lymph nodes.Non specific forms of arteritis and areas of destructive emphysema related to granulomatous inflammation and fibrosis were described. Three cases developed pulmonary hypertension.     

Experimental fungus granuloma as seen from comparative exanthematology

Summary Here is presented a case of the experimental production of fungus granuloma on the ears of rabbits due to a second dorsal inoculation with tr. mentagr., var. ast. This tuberculoid granuloma is preceded or accompanied by fungus phlebitis and occasionally associated with arteritis or perifolliculitis granulomatosa on the ears. These reactions (granuloma, phlebitis, arteritis and perifolliculitis) are regarded as almost certainly falling into a cathegory of trichophytid as demonstrated by histology, serology, trichophytin and blood-cultivation. Also, these reactions are comparable to the cases of human fungus id reactions and tuberculous reinfection lesions in man. Then, similar fungus granulomas were artificially produced on the ears and in both lungs etc. by disseminate reinfection with the tr. ast. via cardiac route in rabbits, which had immunized by a dorsal infection with the tr. Summed up, this work is concerned with experimental fungus granuloma as seen from comparative exanthematology of mycid with other id, tuberculid in particular. We consider the fungus allergic granulomatous reactions as partial manifestations of general immune reaction (including trichophytemia), regardless whether fungi in the lesions activate in loco or result from fungus foci via blood circulation. Also, emphasis is placed upon an evaluation of crude polysaccharide (from the tr. mechanically disintegrated) as antigen or trichophytin (used for serology or trichophytin reaction).Read before the sixth International Congress on Tropical Medicine and Malaria, Division A Section:3 Sub-section: 4-Mycotic Infections —, Lisbon, 5–13 September, 1958.     

Chemical synthesis,expression and mutagenesis of a gene encoding β-cryptogein,an elicitin produced by Phytophthora cryptogea

Elicitins are 10 kDa holoproteins secreted by Phytophthora fungi, that elicit an incompatible hypersensitive reaction, leading to resistance against fungal and bacterial plant pathogens. Comparison of primary sequences of -elicitins and -elicitins indicated several potential necrotic activity-determining residues. All of the highly necrotic -elicitins have a hydrophilic residue (usually lysine) at position 13, whereas in the less necrotic -elicitins this residue is replaced by a valine. Here, we report the synthesis and expression of a gene encoding a highly necrotic elicitin, -cryptogein, and we show that the substitution of Lys-13 of this recombinant protein by a valine leads to a drastic alteration to the necrotic activity of the recombinant protein.     

Sequences and interactions of mycorrhizal fungi on birch

Summary Soil cores collected under a birch tree (Betula pubescens) on an experimental plot showed a progressive change in types of sheathing mycorrhiza with distance from the tree base. Seedlings grown in cores in a glasshouse also developed different mycorrhizal types depending on distance from the tree at which the cores were taken, but the types on seedlings were often different from those in the parent cores. When cores were taken directly beneath fruitbodies and sown to birch in a glasshouse, seedlings developed mycorrhizas of Laccaria, Inocybe and Hebeloma in cores from beneath these fruitbodies, but they seldom developed Lactarius mycorrhizas and never developed Leccinum mycorrhizas in cores taken beneath these fruitbodies. Similarly, when seedlings were grown in soils supplemented with vermiculite-peat inocula in a glasshouse, Laccaria and Hebeloma readily formed mycorrhizas, butLactarius pubescens seldom did so and Leccinum andAmanita muscaria never dit so. Yet all these fungi form mycorrhizas on birch seedlings in aseptic conditions.The results suggest a distinction between early stage and late stage mycorrhizal fungi of birch. Early stage fungi readily infect seedlings from resident or introduced inoculum in normal, unsterile soil, whereas late stage fungi do not readily form mycorrhizas in these conditions.     

Red grain mycetoma of the scalp (Actinomadura pelletieri). A case report from India

A case of red grain mycetoma on the scalp is described. The disease, caused by Actinomadura pelletieri, is extremely rare in this part of the world, and from India this is perhaps the first case with scalp involvement. The lesion showed satisfactory response to partial excision followed by chemotherapy with streptomycin.Mycetoma is a clinical syndrome of localized indolent deforming tumid lesions and sinuses involving the cutaneous and subcutaneous tissues (8). The disease is caused by two groups of agents; one bacterial and the orher fungal and is accordingly classified as actinomycotic and eumycotic mycetoma respectively. The lesions discharging fungal microcolonies referred to as grains usually occur on the foot or the hand. Occasionally, the lesions have been seen on the axillary (3) and the thoracocervical region (6). The involvement of the scalp is extremely rare. Reddy et al (7) in their study of 50 cases from Southern India, found only one instance of a scalp infection, the causative agent being A. madurae. We report herein on a patient with classical lesions of mycetoma on the scalp as a result of Actinomadura pelletieri infection.     

Quantitative estimation of the surface carbohydrates on the infection structures of rust fungi with enzymes and lectins

Lectins of Triticum vulgaris (WGA), Concanavalia ensiformis (ConA), Phaseolus vulgaris (PHA), Lotus tetragonolobus (LTA), Arachis hypogaea (PNA), Ricinus communis (RCA I), Griffonia simplicifolia (GSA II) and the enzymes endo-(13)--D-glucanase, exo-(13)--D-glucanase and laminarinase were tested for binding to the infection structures of Puccinia coronata and Uromyces appendiculatus. The enzymes and lectins were labeled with fluorescein and the fluorescence was measured with a microscope photometer. GSA II and ConA bound to all parts of the two rust fungi to a certain extent. The germ tubes of P. coronata bound at least two times more WGA than did the germ tubes of U. appendiculatus. The appressoria of both rust fungi additionally bound exo-(13)--glucanase, endo-(13)--glucanase and laminarinase. The substomatal vesicle and the infection hypha of both rust fungi mainly bound the glucanases. Furthermore, the substomatal vesicle of U. appendiculatus bound PHA. No obvious binding with LTA, RCA I and PNA was observed. Binding generally could be inhibited by appropriate haptens. Binding to uredospores generally appeared unspecific. The results indicate that the germ tubes have chitin on their outer surfaces, the appressoria chitin and glucans and the substomatal vesicles and infection hyphae mainly glucans. Compared to P. coronata, U. appendiculatus has more terminal linked glucose residues or the glucan has more (13)--linkages. Also, U. appendiculatus has N-acetylgalactosamine or a similar sugar on the surface of the substomatal vesicle.Abbreviations ConA Concanavalia ensiformis agglutinin - FITC fluorescein isothiocyanate - GSA II Griffonia simplicifolic agglutimin II - LTA Lotus tetragonolobus agglutinin - PBS phosphate buffered saline - PNA Peanut agglutinin - RCA I Ricinus communis agglutinin I - PHA Phaseolus vulgaris agglutinin - WGA Wheat germ agglutinin     

IL‐7 suppresses macrophage autophagy and promotes liver pathology in Schistosoma japonicum‐infected mice

In schistosomiasis japonica and mansoni, parasite eggs trapped in host liver elicit severe liver granulomatous inflammation that subsequently leads to periportal fibrosis, portal hypertension, haemorrhage or even death. Macrophages are critical for granuloma formation and the development of liver fibrosis during schistosomiasis. However, whether the aberrant regulation of macrophage autophagy has an effect on the development of liver immunopathology in schistosomiasis remains to be elucidated. In this study, we showed that Schistosoma japonicum (S. japonicum) egg antigen (SEA)‐triggered macrophage autophagy limited the development of pathology in host liver. However, engagement of IL‐7 receptor (IL‐7R/CD127) on macrophages by S. japonicum infection‐induced IL‐7 significantly suppressed SEA‐triggered macrophage autophagy, which led to an enhanced liver pathology. In addition, anti‐IL‐7 neutralizing antibody or anti‐CD127 blocking antibody treatment increased macrophage autophagy and suppressed liver pathology. Finally, we demonstrated that IL‐7 protects macrophage against SEA‐induced autophagy through activation of AMP‐activated protein kinase (AMPK). Our study reveals a novel role for IL‐7 in macrophage autophagy and identifies AMPK as a novel downstream mediator of IL‐7‐IL‐7R signalling and suggests that manipulation of macrophage autophagy by targeting IL‐7‐IL‐7R signalling may have the potential to lead to improved treatment options for liver pathogenesis in schistosomiasis.     

Single gene control of resistance to cutaneous leishmaniasis in mice

A series of inbred, congenic resistant, and hybrid strains of mice were intradermally inoculated with 10⁶ promastigotes of Leishmania tropica. These mice were divided into susceptible and resistant groups using the criteria of lesion size, development of metastatic foci and skin-test reactivity. At 16 weeks of infection, resistant strains A/J, DBA/1J, AKR/J, CBA/J, C3H/HeJ, NZB/BINJ, C57BL/6J, C57BL/10Sn, B10.D2, B10.129(10M), and B10.CE(30NX) had completely resolved their lesions, while susceptible SWR/J and BALB/cJ mice demonstrated large, nonhealing cutaneous lesions. In addition, BALB/cJ developed metastatic lesions on the extremities which progressively increased in size. All BALB/cJ and SWR/J mice died by 7 1/2 months of infection. The BALB/cJ x C57BL/6JF₁ hybrid behaved in an intermediate fashion showing a slower expansion of cutaneous ulcers and a delayed development of metastatic foci, however, the infection ultimately proved fatal. The F₂ generation could be separated into three distinct groups: resistant, intermediate, and susceptible mice with a lesion size distribution pattern in conformity with a 1:2:1 ratio. Male/female susceptibility differences were not noted. These data indicated that development of acquired resistance may be under the control of a single, autosomal gene. The gene did not appear to be H-2-, Ir-2-, or H-11-linked as is seen with Leishmania donovani infections.     

Unusual aspects of granulomatous dermatophytosis

Described are three male patients showing bizarre manifestations of granulomatous dermatophytosis, all in the hand region. One had a small infiltrated nodular lesion near the thumb which was mistaken for a common insect bite. The second had a violaceous-yellowish plaque, also on the thumb, composed of 2–3 small subcutaneous nodules. The third case had five reddish intracutaneous nodules on the dorsum of the hand. Puncture of these nodules revealed the presence of fungal elements and culture yielded T. rubrum in all cases. Each patient was also found to have a fingernail affected by the same agent. Histologic sections in each case showed granulation tissue in the dermis and hypodermis, mainly in the vicinity of hair fragments with spores. These lesions appeared to be variants of Majocchi's granuloma trichophyticum.     

Somatic cell mapping of T-cell receptor CD3 complex and CD8 genes in cattle

Bovine genes encoding T-cell receptor, CD3, and CD8 molecules have been mapped to syntetic groups using bovine × rodent hybrid somatic cells. T-cell receptor and chains were assigned to bovine syntenic group U5, and the and genes were syntenic with each other and with markers on U13. CD3E and CD3D genes were syntenic with each other and located to bovine syntenic group U19. CD8 was most concordant with markers of syntenic group U16, although the concordancy was only 85% and the assignment must be regarded as tentative. The comparative gene maps of human chromosome 7, bovine syntenic group U13, and mouse chromosomes 6 and 13 suggest extensive evolutionary conservation.