Anti- schistosomular activity of human monocytes/macrophages in response to interleukin-3 and granulocyte-macrophage colonystimulating factor stimulation.

Human monocytes, co-incubated for 7 days in culture with GM-CSF or IL-3 but not with IFN-gamma, exerted a variable schistosotnulicidal effect on Schistosoma mansoni parasites when grown in 96-well round-bottomed plates but not in flat-bottomed plates. Addition of LPS or IFN-gamma or both, for the last 48 h did not enhance the cidal effect. Addition of LPS but not IFN-gamma to the pre-incubated cells with GM-CSF or IL-3 markedly stimulated TNF-alpha production by the cells but not their cidal activity. The variable cidal effects obtained with the monocytes/macrophages from different donors suggest that these effects may be genetically predetermined and are possibly linked to blood group markers or to MHC class I or II antigens.

IL-1, TNF-alpha and IL-2 production by peritoneal and spleen cells from Schistosoma mansoni infected mice and its potentiation by preimmunization with schistosomal antigens and immunostimulants.

In the present study we tested the effect of immunization with schistosome derived antigens such as frozen-thawed schistosomula in combination with either BCG, liposomes or liposomal muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE), on the resistance of mice to infection, and on the function of their macrophages and lymphocytes. Immunization with either F-T schistosomula + BCG or F-T schistosomula + MTP-PE and subsequent infection, resulted in a 2-3-fold increase in adherent peritoneal macrophage-mediated schistosomulicidal activity (SCA). Peritoneal and spleen macrophages from immunostimulant treated and/or immunized animals showed a significant increase in LPS triggered TNF-alpha production, as compared to non-treated controls. The highest increase in TNF-alpha production was achieved after immunization with either F-T schistosomula + BCG or F-T schistosomula + MTP-PE. LPS triggered IL-1 production was elevated in spleen and peritoneal macrophages from F-T schistosomula + BCG treated mice, and also in spleen macrophages treated with F-T schistosomula + MTP-PE. Only immunization with F-T schistosomula + BCG increased ConA-induced spleen lymphocyte proliferation and IL-2 production. Immunization of mice with F-T schistosomula + BCG also induced protection against parasite infection, while F-T schistosomula + MTP-PE failed to do so. Potentiation of antischistosomal resistance seems to require both macrophage and lymphocyte activation which was achieved only when BCG served as an immunostimulant.

A first instance of human philophthalmosis in Israel.

Conjunctivitis due to the trematode Philophthalmus in a 13-year-old Israeli girl is described. A single worm, probably a mature Philophthalmus palpebrarum, was detected on the palpebral conjunctiva of the upper eyelid of the right eye. Removal of the worm resulted in rapid abatement of the ocular symptoms. This is the first documentation of human philophthalmosis in Israel.

The schistosomulicidal activity and the production of IL-1 and TNF-alpha by peritoneal macrophages from infected mice and their potentiation by muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) treatment.

Production of TNF-alpha and IL-1 by adherent peritoneal exudate macrophages (APEM) was monitored for 20 weeks in Schistosoma mansoni infected mice in comparison to their schistosomulicidal activity. LPS-triggered IL-1 and TNF-alpha production by APEM peaked 10 weeks post infection (p.i.) and declined thereafter. The schistosomulicidal activity of APEM also peaked after 10 weeks but remained elevated thereafter. Infected mice were also treated with the immunostimulator liposomal muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) 6 or 10 weeks p.i., and their APEM were tested 4 weeks later. APEM from such treated animals showed elevated IL-1 and TNF-alpha production when treatment commenced 6 weeks p.i., while their schistosomulicidal activity increased when treatment commenced either 6 or 10 weeks p.i. The L-arginine inhibitor, NG monomethyl arginine, markedly inhibited the schistosomulicidal activity but not the IL-1 and TNF-alpha production of APEM. Our results show that monokine production increases during the acute phase of infection and declines during its chronic phase, while macrophage schistosomulicidal activity remains constant throughout. Furthermore, TNF-alpha or IL-1 may play a minor role in APEM mediated killing of schistosomula.

Philophthalmus species, probably P. palpebrarum, in Israel: description of the eye fluke from experimental infection.

Following a recent incident of human philophthalmosis in Israel, the intramolluscan larval trematode fauna in snails randomly collected from the suspected water source was checked. Of the snails examined, only Melanopsis praemorsa shed cercariae, including a Philophthalmus cercaria. To identify the philophthalmid species involved, chicks were experimentally infected with metacercariae of the trematode, subsequently yielding mature trematodes resembling those of P. palpebrarum. The majority of trematodes obtained, whether from one-worm infections or from multiple-worm infections resulting in a single trematode in one of the eyes, were relatively small and showed only immature eggs in their uteri. This finding suggests that the existing descriptions of two species of Philophthalmus purportedly harbouring eggs with non-oculate miracidia, namely P. palpebrarum and P. nyrocae, are actually based on immature specimens from one-worm infections that precluded cross-fertilisation. If this be true, then all species of the genus Philophthalmus produce eggs that, when mature, contain oculate miracidia. The species encountered in Israel is thus most likely P. palpebrarum.

On the interaction between macrophages and developmental stages of Schistosoma mansoni: effect of muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) treatment on mice survival and the generation of schistosomulicidal macrophages.

Schistosomiasis is a chronic disease afflicting hundreds of millions of people throughout the world against which there is as yet no effective vaccine. In the present study we tested the effect of the immunomodulator muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) on the survival of Schistosoma mansoni-infected mice and on the induction in them of schistosomulicidal macrophages. Mice exposed to 80 cercariae each and then treated with MTP-PE showed prolonged survival following either single or repeat infection. The treatment with MTP-PE, when initiated 70 days post the schistosome infection, diminished significantly the mortality of infected mice over an observed period of 110 days. In terms of treatment efficacy there was no evident difference between the intravenous and intraperitoneal mode of administration of the drug. MTP-PE treatment significantly reduced granuloma size and markedly diminished liver damaged as judged by the lower levels of alkaline phosphatase in the serum. Such treatment exerted no significant effect on the spleen or liver weight in infected mice nor on the worm burden resulting from either a single or double infection. In infected and non-treated mice, schistosomulicidal macrophages appeared after 8-10 weeks of infection. In infected mice treated with MTP-PE there was an accelerated appearance of such macrophages and these exhibited a greater cidal effect on the schistosomula. These immunostimulatory and life-prolonging effects of MTP-PE on S. mansoni-infected mice might indicate an effect of this reagent on cells involved in the granulomatous process.

On the possible schistosomulicidal effect of macrophage-derived lysozyme.

Lysozyme secretion from macrophages of Schistosoma mansoni-infected mice was time dependent, rising significantly from the 8th week post-infection, the macrophages thereafter exhibiting very high levels (greater than 90%) of schistosomulicidal activity. Despite the ability of lysozyme to kill schistosomula in vitro, the concentrations required for such killing were several hundred-fold to several thousand-fold higher than those detected in the supernatants from infected-mice macrophages cultured with or without schistosomula. An in vitro lysozyme inhibitor, N,N,N-triacetyl chitobiose, did not abrogate the cytotoxic ability of macrophages from schistosome-infected mice, but an inhibitor of arginine-dependent cytotoxicity, NG-monomethyl arginine, markedly inhibited schistosomulicidal activity. Evidently, concentrations of ambient lysozyme from macrophage cultures are too low to affect schistosomula in culture, while the main schistosomulicidal pathway in vitro seems to be arginine dependent.

The hair follicle mites (Demodex spp.). Could they be vectors of pathogenic microorganisms?

The hair follicle mites Demodex folliculorum and D. brevis are the most common permanent ectoparasites of Man. Ordinarily they are harmless to their human host and appear to be of no medical significance. We present, however, an unusual finding regarding this mite, namely, that in a potassium hydroxide mount of a skin scraping from a mycotic plaque we found numerous Demodex mites containing inside them spores of Microsporum canis. This could mean that the putatively inoffensive Demodex has the potential to ingest various microorganisms that are found in its niche and transport them to other areas of the skin or possibly to other individuals.

On the interactions between macrophages and developmental stages of Schistosoma mansoni: the cytotoxic mechanisms involved in macrophage-mediated killing of schistosomula in vitro.

In an in vitro cytotoxicity assay, mouse adherent peritoneal exudate macrophages (APEM), harvested 8-10 weeks post Schistosoma mansoni infection caused sizable (greater than 90%) specific killing of schistosomula. This cidal effect was not diminished by the addition of scavengers of oxidative burst products to the cytotoxicity assay, albeit macrophages from schistosome-infected mice produced more H2O2 than did macrophages from non-infected mice. Of inhibitors of lysosomal enzyme function and release added to the cytotoxicity assay, trypan blue (1 mg/ml) fully abolished the schistosomulicidal effect; hydrocortisone (100 micrograms/ml) was partly effective, and gold salts (1 mg/ml) were ineffective. A cidal effect was not apparent in the absence of L-arginine nor in the presence of excess (greater than 400 micrograms/ml) L-arginine, L-lysine or L-ornithine. Arginase (5 U/ml) totally abrogated the schistosomulicidal effect. The findings suggest that a macrophage protein of a lysosomal origin, dependent on arginine for its reaction and/or production, may be involved in the in vitro killing of schistosomula by macrophages from S. mansoni-infected mice.

Intraocular pentastomiasis causing unilateral glaucoma.

We present a case of intraocular pentastomiasis in a 12-year-old Israel Arab boy. A single secondary pentastomid larva, most likely of Linguatula serrata, was found in the anterior chamber of the right eye, attached loosely to the pupil's border by a fibrinous mass. Associated conditions were iritis, subluxation of the lens, and secondary glaucoma. This is the first documentation of human pentastomiasis in Israel.

The interactions between macrophages and developmental stages of Schistosoma mansoni: effect of macrophage function modulators on the viability of S. mansoni in vivo and in vitro.

ICR mice infected with Schistosoma mansoni developed sizable concomitant immunity to a challenge infection 10 weeks, but not 7 weeks, following the primary infection. At 7 weeks, postprimary-infection mice exhibited increased resistance to reinfection when treated with BCG or MDP. BCG even rendered noninfected mice resistant to infection. Macrophage function inhibitors such as silica and trypan blue did not abolish the concomitant immunity state, but they increased the worm burden due to a single infection, whether given before or after the infection. The onset of concomitant immunity in infected mice was paralleled by the appearance in their peritoneal exudate of schistosomulicidal-adherent macrophages. Such cells were evident at 9 but not 7 weeks of infection. The in vivo injection of MDP accelerated their appearance in infected mice, while silica, trypan blue, and carrageenan abolished it. The findings suggest that highly activated schistosomulicidal macrophages develop in infected mice, and might participate in the destruction of the invading parasite.

Immunological aspects of murine infection with the rat nematode Strongyloides ratti Sandground, 1925.

In a study of the immune response of the rat to infection with the nematode Strongyloidis ratti, the antigens of the infective larval stage (L3) and of the parasitic, parthenogenetic female (Fp) were investigated. From both the larvae and the adult females, one metabolic (exoantigen) and two somatic antigens were extracted. Of the two somatic antigens, one was soluble and obtainable by physical means while the other was separated by chemical means from the tegument of the parasite. Humoral responses to the various antigens were evaluated by immunodiffusion and ELISA techniques, while the overall immune response was assayed by the worm burden in the immunized and subsequently infected rats. Agar-gel double diffusion yielded precipitin bands only with larval somatic antigens. ELISA proved positive at a titer of 20,000 with larval metabolic antigen and sera of rats immunized against either larval metabolic or somatic antigens. By 20 days post challenge infection, however, this titer diminished to 4000. In vivo studies of worm burden in rats immunized with the various antigens and then exposed to the live L3 of the nematode showed that there were significantly fewer adult worms in the rats immunized with larval somatic antigen and adult metabolic antigen than in those immunized with adult somatic antigen or larval metabolic antigen.

Human pleuropulmonary gnathostomiasis: a case report from Israel.

We report a case of human gnathostomiasis presenting with bilateral pleural effusion and probable pericardial involvement. The diagnosis was made on the basis of the patient's country of origin (Nepal), the course of the disease, marked eosinophilia and the identification of Gnathostoma in a thoracic skin biopsy. The patient responded, presumably, to treatment with diethylcarbamazine (Hetrazan). This case is unique in its presentation and occurrence in Israel (although not necessarily acquired in Israel).