Host-Specific Serum Factors Control the Development and Survival of Schistosoma mansoni

IntroductionSchistosomiasis is a neglected tropical disease (NTD) caused by blood-dwelling flatworms which develop from skin-penetrating cercariae, the freely swimming water-borne infective stage of Schistosoma mansoni, into adult worms. This natural course of infection can be mimicked in experimental mouse models of schistosomiasis. However, only a maximum of 20-30% of penetrated cercariae mature into fecund adults. The reasons for this are unknown but could potentially involve soluble factors of the innate immune system, such as complement factors and preexisting, natural antibodies.Materials and MethodsUsing our recently developed novel serum- and cell-free in vitro culture system for newly transformed schistosomula (NTS), which supports long-term larval survival, we investigated the effects of mouse serum and its major soluble complement factors C1q, C3, C4 as well as preexisting, natural IgM in vitro and assessed worm development in vivo by infecting complement and soluble (s)IgM-deficient animals.ResultsIn contrast to sera from humans and a broad variety of mammalian species, serum from mice, surprisingly, killed parasites already at skin stage in vitro. Interestingly, the most efficient killing component(s) were heat-labile but did not include important members of the perhaps best known family of heat-labile serum factors, the complement system, nor consisted of complement-activating natural immunoglobulins. Infection of complement C1q and sIgM-deficient mice with S. mansoni as well as in vitro tests with sera from mice deficient in C3 and C4 revealed no major role for these soluble factors in vivo in regard to parasite maturation, fecundity and associated immunopathology. Rather, the reduction of parasite maturation from cercariae to adult worms was comparable to wild-type mice.ConclusionThis study reveals that not yet identified heat-labile serum factors are major selective determinants of the host-specificity of schistosomiasis, by directly controlling schistosomal development and survival.

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Artificially transformed schistosomula of Schistosoma mansoni: mechanism of acquisition of protection against antibody-mediated killing

Parasitology ◽

10.1017/s0031182000000548 ◽

1980 ◽

Vol 80 (1) ◽

pp. 95-104 ◽

Cited By ~ 28

Author(s):

C. A. P. Tavares ◽

M. N. Cordeiro ◽

T. A. Mota-Santos ◽

G. Gazzinelli

Keyword(s):

Amino Acid ◽

Schistosoma Mansoni ◽

Gel Electrophoresis ◽

Polyacrylamide Gel Electrophoresis ◽

Rabbit Serum ◽

Normal Rabbit Serum ◽

Serum Factors ◽

Quantitative Fluorescence

SummaryIncorporation of labelled amino acid into tegumental proteins and acquisition of protection by schistosomula against antibody-mediated killing in vitro were simultaneously stimulated by serum factors and inhibited by puromycin. Comparison of polyacrylamide gel electrophoresis patterns with fluorographic autoradiography indicates that the majority of proteins in the parasite tegument were labelled with the isotope after incubation for 3 h. No new, clearly defined band was observed in the autoradiography pattern. During this period a decreasing susceptibility of the schistosomula to antibody plus complement was observed. Quantitative fluorescence assay shows that schistosomula insensitive to antibody plus complement were still able to bind the same amount of antibody as the unprotected parasites. Pre-culture of schistosomula in the presence of inactivated normal rabbit serum also decreased the susceptibility of the parasites to the in vivo killing mechanism.

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Faculty Opinions recommendation of Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1018413.209475 ◽

2004 ◽

Author(s):

Paul J Brindley

Keyword(s):

Schistosoma Mansoni ◽

Praziquantel Treatment

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Novel Role for Albumin in Innate Immunity: Serum Albumin Inhibits the Growth of Blastomyces dermatitidis Yeast Form In Vitro

Infection and Immunity ◽

10.1128/iai.71.11.6648-6652.2003 ◽

2003 ◽

Vol 71 (11) ◽

pp. 6648-6652 ◽

Cited By ~ 12

Author(s):

Steven Giles ◽

Charles Czuprynski

Keyword(s):

Molecular Weight ◽

Inhibitory Activity ◽

Mammalian Species ◽

Blastomyces Dermatitidis ◽

Low Molecular Weight ◽

Rat Serum ◽

Yeast Form ◽

Domain Iii

ABSTRACT In this study we found that serum inhibitory activity against Blastomyces dermatitidis was principally mediated by albumin. This was confirmed in experiments using albumin from several mammalian species. Analbuminemic rat serum did not inhibit B. dermatitidis growth in vivo; however, the addition of albumin restored inhibitory activity. Inhibitory activity does not require albumin domain III and appears to involve binding of a low-molecular-weight yeast-derived growth factor.

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Opioids and testicular activity in the frog, Rana esculenta

Journal of Endocrinology ◽

10.1677/joe.0.1370049 ◽

1993 ◽

Vol 137 (1) ◽

pp. 49-NP ◽

Cited By ~ 19

Author(s):

F. Facchinetti ◽

A. R. Genazzani ◽

M. Vallarino ◽

M. Pestarino ◽

A. Polzonetti-Magni ◽

...

Keyword(s):

Physiological Activity ◽

Mammalian Species ◽

Rana Esculenta ◽

Cell Degeneration ◽

Efferent System ◽

Naltrexone Treatment ◽

Nucleus Infundibularis ◽

The Brain

ABSTRACT The presence and activity of brain, pituitary and testicular β-endorphin (β-EP)-like material have been studied in the frog, Rana esculenta, using reverse-phase high-pressure liquid chromatography, coupled with radioimmunoassay and immunocytochemistry. In-vivo and in-vitro treatments with naltrexone were carried out to assess the putative physiological activity of opioid peptides. β(1–31) and (1–27), together with their acetylated forms, have been identified in brain, pituitary and testis. In particular, β-EP(1–31) concentrations peaked during July in the brain and pituitary, whilst in testes maximum concentrations were found in April and November. β-EP immunoreactivity was present in the brain within the nucleus preopticus and nucleus infundibularis ventralis while positive fibres in the retrochiasmatic regions projected to the median eminence. In the testis, interstitial cells, canaliculi of the efferent system, spermatogonia and spermatocytes showed positive immunostaining for β-EP. In intact animals, naltrexone treatment increased plasma and testicular androgen levels and this effect was confirmed in in-vitro incubations of minced testes. Naltrexone also induced a significant increase in germ cell degeneration. Our results indicated that an opioid system modulates the hypothalamus-pituitary-gonadal axis in the frog, Rana esculenta and, for the first time, we have shown that the testicular activity of a non-mammalian species may be regulated by opiates locally. Journal of Endocrinology (1993) 137, 49–57

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In vitro and in vivo studies of the effect of artemether on Schistosoma mansoni.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.33.9.1557 ◽

1989 ◽

Vol 33 (9) ◽

pp. 1557-1562 ◽

Cited By ~ 93

Author(s):

S H Xiao ◽

B A Catto

Keyword(s):

Schistosoma Mansoni ◽

In Vivo Studies

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Myosin light-chain 1 and 3 gene has two structurally distinct and differentially regulated promoters evolving at different rates

Molecular and Cellular Biology ◽

10.1128/mcb.5.11.3168-3182.1985 ◽

1985 ◽

Vol 5 (11) ◽

pp. 3168-3182

Author(s):

E E Strehler ◽

M Periasamy ◽

M A Strehler-Page ◽

B Nadal-Ginard

Keyword(s):

Light Chain ◽

Myosin Light Chain ◽

Mammalian Species ◽

In Vitro Transcription ◽

Chain Gene ◽

Promoter Regions ◽

Light Chain Gene ◽

Direct Initiation

DNA fragments located 10 kilobases apart in the genome and containing, respectively, the first myosin light chain 1 (MLC1f) and the first myosin light chain 3 (MLC3f) specific exon of the rat myosin light chain 1 and 3 gene, together with several hundred base pairs of upstream flanking sequences, have been shown in runoff in vitro transcription assays to direct initiation of transcription at the cap sites of MLC1f and MLC3f mRNAs used in vivo. These results establish the presence of two separate, functional promoters within that gene. A comparison of the nucleotide sequence of the rat MLC1f/3f gene with the corresponding sequences from mouse and chicken shows that: the MLC1f promoter regions have been highly conserved up to position -150 from the cap site while the MLC3f promoter regions display a very poor degree of homology and even the absence or poor conservation of typical eucaryotic promoter elements such as TATA and CAT boxes; the exon/intron structure of this gene has been completely conserved in the three species; and corresponding exons, except for the regions encoding most of the 5' and 3' untranslated sequences, show greater than 75% homology while corresponding introns are similar in size but considerably divergent in sequence. The above findings indicate that the overall structure of the MLC1f/3f genes has been maintained between avian and mammalian species and that these genes contain two functional and widely spaced promoters. The fact that the structures of the alkali light chain gene from Drosophila melanogaster and of other related genes of the troponin C supergene family resemble a MLC3f gene without an upstream promoter and first exon strongly suggests that the present-day MLC1f/3f genes of higher vertebrates arose from a primordial alkali light chain gene through the addition of a far-upstream MLC1f-specific promoter and first exon. The two promoters have evolved at different rates, with the MLC1f promoter being more conserved than the MLC3f promoter. This discrepant evolutionary rate might reflect different mechanisms of promoter activation for the transcription of MLC1f and MLC3f RNA.

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Functional domains of the pp60v-src protein as revealed by analysis of temperature-sensitive Rous sarcoma virus mutants

Molecular and Cellular Biology ◽

10.1128/mcb.4.8.1508-1514.1984 ◽

1984 ◽

Vol 4 (8) ◽

pp. 1508-1514

Author(s):

A W Stoker ◽

P J Enrietto ◽

J A Wyke

Keyword(s):

Rous Sarcoma Virus ◽

Kinase Activity ◽

Temperature Sensitive ◽

Tyrosine Kinase Activity ◽

Rous Sarcoma ◽

Heat Labile ◽

Src Gene ◽

Sarcoma Virus

Four temperature-sensitive (ts) Rous sarcoma virus src gene mutants with lesions in different parts of the gene represent three classes of alteration in pp60src. These classes are composed of mutants with (i) heat-labile protein kinase activities both in vitro and in vivo (tsLA27 and tsLA29), (ii) heat-labile kinases in vivo but not in vitro (tsLA33), and (iii) neither in vivo nor in vitro heat-labile kinases (tsLA32). The latter class indicates the existence of structural or functional pp60src domains that are required for transformation but do not grossly affect tyrosine kinase activity.

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