DC-SIGN mediates the binding of Aspergillus fumigatus and keratinophylic fungi by human dendritic cells

Human contact with fungi does not usually lead to pathological consequences, as the immune system manages to defeat the invader pathogens. Nevertheless, under immune suppression, fungi overcome immune defenses and cause diseases that range from nonserious colonizations of keratinizated tissue (Dermatophytosis) to life threatening disseminated infections (Aspergillosis). Host defenses against fungi rely on innate and adaptative responses, with dendritic cell (DC) and macrophage surface receptors having a major role in the recognition of fungal pathogens and in the orchestration of an effective immune response. DC-SIGN is a C-type lectin involved in the recognition of bacterial, viral and parasitic pathogens, as well as in interactions between cells of the immune system. Its expression is restricted to DCs and subsets of macrophages. Here we show that DC-SIGN mediates the binding and capture of Aspergillus fumigatus and keratinophylic fungi, including Chrysosporium tropicum, by human DCs, describe the requirements of these interactions and discuss their potential involvement in the onset and persistence of pulmonary fungal infections.     

Decreased availability of intestinal dopamine in transmural colitis may relate to inhibitory effects of interferon-gamma upon L-DOPA uptake

AIMS: The present study aimed to evaluate the relationship between intestinal inflammation, interferon-gamma (IFN-gamma) levels and intestinal levels of dopamine, its precursor l-3,4-dihydroxyphenylalanine (L-DOPA), and the activity of aromatic L-amino acid decarboxylase (AADC) activity along the digestive tract in a rat experimental model of colitis. METHODS: Colitis was induced by rectal administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS). Catechol derivatives were assayed by means of HPLC-EC. RESULTS: It is shown that dopamine and noradrenaline levels in the distal colon (inflamed mucosa), but not in the ileum (non-inflamed mucosa), of TNBS-treated rats were markedly lower than in control animals. A slight decrease in L-DOPA tissue levels, no changes in AADC activity and an increase in plasma IFN-gamma levels accompanied this decrease in dopamine levels. Exposure of Caco-2 cells, a human intestinal epithelial cell line, to human IFN-gamma resulted in a concentration-dependent and long-lasting inhibition of L-DOPA uptake, which most likely explains the decrease in dopamine levels in the inflamed mucosa. CONCLUSION: Changes in tissue levels of noradrenaline and dopamine in experimental colitis in the rat follow a similar pattern to that observed in patients with Crohn's disease and ulcerative colitis. In this model of experimental colitis, the decrease in dopamine levels is most likely explained by the inhibitory effect of IFN-gamma on L-DOPA uptake by intestinal epithelial cells.     

Intermittent preventive sulfadoxine-pyrimethamine treatment of primigravidae reduces levels of plasma immunoglobulin G, which protects against pregnancy-associated Plasmodium falciparum malaria

Pregnancy-associated malaria (PAM) is an important cause of maternal and neonatal suffering. It is caused by Plasmodium falciparum capable of inhabiting the placenta through expression of particular variant surface antigens (VSA) with affinity for proteoglycans such as chondroitin sulfate A. Protective immunity to PAM develops following exposure to parasites inhabiting the placenta, and primigravidae are therefore particularly susceptible to PAM. The adverse consequences of PAM in primigravidae are preventable by intermittent preventive treatment (IPTp), where women are given antimalarials at specified intervals during pregnancy, but this may interfere with acquisition of protective PAM immunity. We found that Kenyan primigravidae receiving sulfadoxine-pyrimethamine IPTp had significantly lower levels of immunoglobulin G (IgG) with specificity for the type of parasite-encoded VSA-called VSA(PAM)-that specifically mediate protection against PAM than did women receiving a placebo. VSA(PAM)-specific IgG levels depended on the number of IPTp doses received and were sufficiently low to be of clinical concern among multidose recipients. Our data suggest that IPTp should be extended to women of all parities, in line with current World Health Organization recommendations.     

Sporogony and experimental transmission of Babesia equi by Boophilus microplus

The development of Babesia equi in salivary glands of adult female Boophilus microplus was observed under a light microscope using semithin sections stained with toluidine blue. Engorged nymphs were obtained from splenectomized foals experimentally infected with B. equi. As adults, they were then fed on rabbits for 5 days and the salivary glands of manually collected individuals were removed at intervals of 24 h. Sporozoites were found in type III granular acini cells between the 2nd and 5th days following feeding on the rabbits. Sporoblasts and sporozoites were observed in the same or adjacent acini cells in all the glands examined. The formation of the sporozoites occurred following the multiple division of the sporoblasts through a process of radial budding from the periphery of bodies resulting from multiple fission. Sporozoites were detected in smears of adult males stained with Giemsa, between the 2nd and 5th days following feeding by the ticks. Adults of B. microplus, fed during the nymphal phase on foals with patent parasitemia, transmitted sporozoites of B. equi to a splenectomized foal. The role of B. microplus in the transmission and epidemiology of B. equi is discussed. Received: 16 June 1997 / Accepted: 2 September 1997     

Cervical muscle response to trunk flexion in whiplash-type lateral impacts

The purpose of this study was to determine the response of the cervical muscles to increasing low-velocity, whiplash-type lateral impacts when the occupant is seated out of the recommended driving position (neutral posture). Twenty healthy volunteers were subjected to left lateral impacts of 4.1, 7.7, 10.5, and 13.7 m/s² acceleration, with their trunk flexed by 45° and laterally flexed to the right and left also by 45° at the time of impact. Bilateral electromyograms of the sternocleidomastoids, trapezii, and splenii capitis were recorded. Under these conditions of trunk-flexed postures, in a left lateral impact, muscle responses were of generally low magnitude with the trunk flexed to either the left or right. Even at the highest acceleration of 13.7 m/s², all muscles generated less than 37% of their known maximal voluntary contraction electromyogram. Also, in these left lateral impacts, the right splenius capitis showed a greater EMG response than the left splenius capitis regardless of whether the subject was flexed to the right or left at the time of impact. The right splenius capitis (the one contralateral to the left lateral impact direction) was more active than its counterpart. Compared to what is known for EMG responses with an occupant in the neutral posture, the right sternocleidomastoid (usually the most active muscle in a left lateral collision) was significantly less-active with trunk flexion than with neutral posture conditions (P<0.01). In the absence of bodily impact, the flexed trunk posture does not produce a biomechanical response that would increase the likelihood of cervical muscle injury in low velocity lateral impacts, and may lessen the risk of injury for some muscles.     

Participation of serum and membrane lectins on the oxidative burst regulation in Macrobrachium rosenbergii hemocytes

Using a spectrophotometric NBT reduction assay and phagocytosis, we identified that production of superoxide anions and phagocytic activity of hemocytes from Macrobrachium rosenbergii were significantly higher in the presence of rat, rabbit, and chicken erythrocytes than with human, pig, or horse erythrocytes. Hemocytes stimulated with MrL, MrLMab, or PMA increased 4.7, 5.1, and 6.1 fold, respectively, the oxidative response as compared to non-stimulated hemocytes. MrLMab together with MrL increased 5.7 fold the oxidative capacity of hemocytes as compared to non-stimulated cells. These effects were inhibited with 100 mM GalNAc, GlcNAc, or Neu5Ac and 0.2 microM of sialylated submaxillary gland mucin and fetuin. Piroxicam inhibited (P < 0.05) the production of O(2)(-) induced by MrL, whereas iodoacetamide inhibited the effect of MrLMAb (P < 0.05) in a dose-dependent manner. Our results suggest that MrLMab might activate the oxidative burst through the metabolism of glucose as opposed to MrL which utilizes NADPH-independent mechanisms, very probably through pro-inflammatory metabolites.     

Trypanosoma cruzi: Killing and enhanced uptake by resident peritoneal macrophages treated with alpha-2-macroglobulin

We report that alpha-2-macroglobulin (A2M), the physiologically important plasma protease inhibitor and suspected immunomodulator, alters the functional ability of murine resident peritoneal macrophages (RM) to ingest and kill the infective trypomastigote stage ofTrypanosoma cruzi, the aetiological agent of Chagas' disease. Treatment of RM with 500 g/ml A2M for 30 min enhanced the uptake of trypomastigotes, epimastigotes, and amastigotes by 125%, 46%, and 300%, respectively. The same treatment also increased the phagocytosis of sheep erythrocytes opsonized with complement and IgG as well as of galactosylated asialoerythrocytes. After 60–90 min parasite-cell interaction, epi-and amastigotes were killed by the RM, whereas the infection with trypomastigotes was controlled only after 24 h. Other protease inhibitors, bovine serum albumin, and LPS showed no such effect. The production of hydrogen peroxide was not affected by A2M treatment, but the ultrastructural aspects showed trypomastigote damage and enhancement of macrophage membrane ruffling, indicative of macrophage activation. These results suggest that A2M has the ability to modulate, at least functionally, certain receptor-mediated endocytic pathways that, in concert with an activation of possibly oxygen-independent microbicidal mechanisms, could contribute to resistance against the parasite.Abbreviations A2M alpha-2-macroglobulin - F-A2M fast A2M - S-A2M slow A2M - RM resident macrophages - BT bloodstream trypomastigotes - EPI epimastigotes - AMA amastigotes - DMEM Dulbecco's Modified Eagle Medium - PBS phosphate-buffered saline - BSA bovine serum albumin - LPS bacto lipopolysaccharide - STI sovoean trypsin inhibitor - PPA pepstatin A - LPT leupeptin - PNT 1, 10-phenanthroline - TLCK N--tosy-L-lysine-chloromethylketone - E sheep erythrocyte - aE asialoerythrocyte - Gal R receptors for galactosylated particles     

Vagotomy reduces obesity in MSG-treated rats

In order to study the role of vagus nerve activity at the onset of obesity induced by monosodium glutamate (MSG), 30-day-old MSG-rats were vagotomized or sham operated. Body weight and food intake were recorded until animals were 90 days old and then sacrificed. Naso-anal length was recorded for all animals. Periepididymal and retroperitoneal fat pads were isolated and weighed. Reduction of body weight and naso-anal length were registered in 30-day-old MSG-rats. Obesity could also be observed, as increase of Lee index indicated. Results were most evident in 90-day-old MSG-rats. In both groups neither body weight gain nor food intake was changed by vagotomy. However, fat accumulation on tissues was reduced by vagotomy in MSG-rats. The results showed that MSG-obesity is not related to an increment in food intake behavior. Vagotonia might play a role at the onset of MSG-obesity.