RÉSUMÉ
Macrophages are host cells for parasites of the genus Leishmania where they multiply inside parasitophorous vacuoles. Paradoxically, macrophages are also the cells responsible for killing or controlling parasite growth, if appropriately activated. In this review, we will cover the patterns of macrophage activation and the mechanisms used by the parasite to circumvent being killed. We will highlight the impacts of the vector bite on macrophage activation. Finally, we will discuss the ontogeny of macrophages that are infected by Leishmania spp.
Sujet(s)
Cytokines/métabolisme , Leishmaniose/métabolisme , Leishmaniose/parasitologie , Macrophages/métabolisme , Macrophages/parasitologie , Animaux , Humains , Leishmania/pathogénicité , Activation des macrophages/physiologieRÉSUMÉ
Proteasomes are multisubunit proteases that exist universally among eukaryotes. They have multiple proteolytic activities and are believed to have important roles in regulating cell cycle, selective intracellular proteolysis, and antigen presentation. Here we have partially purified Leishmania chagasi proteasome. The L. chagasi proteasome rich fraction displayed the typical features of eukaryotic 20S proteasome complexes, being active towards peptidyl substrates with hydrophobic and acidic residues, and sensitive to the proteasome-specific inhibitor lactacystin. We have shown that lactacystin, or its active form clasto-lactacystin beta-lactone, but not E-64, blocks the in vitro growth of L. chagasi promastigotes, demonstrating that the interference with parasite growth is due to the lack of proteasome activity. Furthermore, pre-treatment of L. chagasi promastigotes with lactacystin did not prevent parasite entry in host cells, but markedly restricted its intracellular survival. These results demonstrate that intact parasite proteasome function is required for replication of L. chagasi and for amastigotes survival inside the vertebrate host cell.
Sujet(s)
Acétylcystéine/analogues et dérivés , Cysteine endopeptidases/métabolisme , Leishmania/enzymologie , Leishmaniose viscérale/parasitologie , Leucine/analogues et dérivés , Macrophages péritonéaux/parasitologie , Complexes multienzymatiques/métabolisme , Acétylcystéine/pharmacologie , Animaux , Coumarines/métabolisme , Cysteine endopeptidases/isolement et purification , Inhibiteurs de la cystéine protéinase/pharmacologie , Modèles animaux de maladie humaine , Leishmania/croissance et développement , Leishmania/métabolisme , Leucine/pharmacologie , Mâle , Souris , Complexes multienzymatiques/antagonistes et inhibiteurs , Complexes multienzymatiques/isolement et purification , Oligopeptides/métabolisme , Fluorure de phénylméthanesulfonyle/pharmacologie , Proteasome endopeptidase complexRÉSUMÉ
BACKGROUND: The success of PCR technique depends on many factors, such as high quality DNA pellets obtained from blood samples, good reagents and adequate conditions of amplification. Taking these limitations into account, a retrospective epidemiological study for malaria diagnosis was conducted in a mesoendemic area in the Brazilian Amazon. METHODS: A nested PCR protocol with DNA extracted from two blood storage devices obtained from Giemsa-stained thick blood smears and filter-papers was used for malaria diagnosis. The extracted DNA was used as a template to amplify approximately 100 bp species-specific sequences of the small subunit of the ribosomal RNA (18S SSU rRNA) of Plasmodium sp. The prevalence of single and mixed infections was examined in a cross-sectional survey carried out among 369 miners living in the district of Apiacás, Mato Grosso State. The parasitemia levels detected by microscopic examination were compared to the PCR results. RESULTS: DNA samples isolated from blood on filter-paper allowed the detection and identification of Plasmodium in 165 (44.7%) of the 369 individuals evaluated, while only 62 (16.8%) had positive results using DNA obtained from thick smears, a similar rate observed by microscopic examination. The sensitivities of PCR using DNA from blood smears and filter-papers were 65% and 73.0%, respectively. Low parasite infections (below 20 parasites/ micro L blood) were not detected when thick blood smears were used as a DNA source. CONCLUSIONS: Although the blood preserved as thick blood smears provides an alternative and useful tool for malaria molecular diagnosis, its relatively poor performance at low level parasitemias impairs the correct determination of malaria prevalence in epidemiological studies. However, the results obtained in the present study confirm that the use of filter-paper to collect blood is useful for field studies.
Sujet(s)
ADN des protozoaires/sang , Paludisme/épidémiologie , Parasitémie/épidémiologie , Plasmodium/isolement et purification , Réaction de polymérisation en chaîne/normes , Animaux , Prélèvement d'échantillon sanguin/méthodes , Brésil/épidémiologie , Études transversales , ADN ribosomique/sang , ADN ribosomique/classification , Humains , Paludisme/diagnostic , Parasitémie/diagnostic , Parasitémie/parasitologie , Plasmodium/génétique , Prévalence , ARN ribosomique 18S/génétique , Études rétrospectives , Sensibilité et spécificitéRÉSUMÉ
Tumor necrosis factor-stimulated gene 14 (TSG-14)/PTX3 was identified originally as a TNF-alpha and IL-1beta-stimulated gene from normal, human foreskin fibroblasts and vascular endothelial cells, respectively. TSG-14 gene encodes a 42-kDa-secreted glycoprotein with a carboxy-terminal half that shares homology with the entire sequence of C-reactive protein (CRP) and serum amyloid P component (SAP), acute-phase proteins of the pentraxin family. Some experimental evidence suggests that TSG-14 plays a role in inflammation, yet its function and mechanism of action remain unclear. We have generated transgenic mice that overexpress the murine TSG-14 gene under the control of its own promoter. From eight transgenic founders, two lineages were derived and better characterized: Tg2 and Tg4, carrying two and four copies of the transgene, respectively. TSG-14 transgenic mice were found to be more resistant to the endotoxic shock induced by LPS and to the polymicrobial sepsis caused by cecal ligation and puncture (CLP). Moreover, macrophages derived from the transgenic mice produced higher amounts of nitric oxide in response to IFN-gamma, TNF-alpha, and LPS as compared with macrophages from wild-type animals, and the augmented response appears to be the consequence of a higher responsiveness of transgenic macrophages to IFN-gamma. The data shown here are the first in vivo evidence of the involvement of TSG-14 in the inflammatory process and suggest a role for TSG-14 in the defense against bacterial infections.
Sujet(s)
Protéine C-réactive/physiologie , Endotoxémie/génétique , Sepsie/génétique , Composant sérique amyloïde P/physiologie , Animaux , Lignées animales non consanguines , Protéine C-réactive/génétique , Caecum/traumatismes , Caecum/microbiologie , Modèles animaux de maladie humaine , Endotoxémie/immunologie , Humains , Immunité innée , Inflammation , Interféron gamma/pharmacologie , Perforation intestinale/complications , Ligature , Lipopolysaccharides/toxicité , Activation des macrophages/effets des médicaments et des substances chimiques , Macrophages péritonéaux/effets des médicaments et des substances chimiques , Macrophages péritonéaux/physiologie , Souris , Souris transgéniques , Monoxyde d'azote/biosynthèse , Protéines de fusion recombinantes/physiologie , Sepsie/étiologie , Sepsie/immunologie , Composant sérique amyloïde P/génétique , Facteur de nécrose tumorale alpha/pharmacologieRÉSUMÉ
We have previously shown that both promastigotes and amastigotes of Leishmania amazonensis contain a lytic protein that damages erythrocytes and nucleated cells, including macrophages (F. S. M. Noronha, F. J. Ramalho-Pinto, and M. F. Horta, Infect. Immun. 64:3975-3982, 1996). Using the patch-clamp technique, we show here that cell damage by parasite extracts is mediated by the formation of nonselective pores on the target membrane. This demonstrates that L. amazonensis cytolysin is a pore-forming protein (PFP), here named leishporin. We show that the diameters of the pores formed by parasite extracts are heterogeneous, varying from approximately 1.6 to >6.1 nm according to cytolysin concentration or time. We also show that pore formation involves the binding of the PFP to the target cell membrane, a temperature-independent event that is necessary but not sufficient to lyse cells. This is followed by a temperature-dependent step that triggers lysis, probably the insertion and the polymerization of protein subunits in the lipid bilayer. We provide evidence that suggests that polymerization of single subunits must occur for pore formation. We show, in addition, that L. amazonensis expresses molecules antigenically homologous to other PFPs.
Sujet(s)
Membrane cellulaire/effets des médicaments et des substances chimiques , Cytotoxines/pharmacologie , Leishmania/pathogénicité , Macrophages/effets des médicaments et des substances chimiques , Protéines de protozoaire/pharmacologie , Animaux , Conductivité électrique , Souris , Techniques de patch-clampRÉSUMÉ
Crude extracts of Leishmania amazonensis, but not of L. guyanensis, are lytic to erythrocytes and nucleated cells, including macrophages. L. amazonensis-mediated lysis is caused by a membrane-associated pore-forming protein, named a-leishporin. Here we show that L. amazonensis, but not L. guyanensis, promastigote extracts increase their hemolytic activity when kept at 4 degrees C for a few days or at 37 degrees C for a few hours. We show that the activation in the extracts is mediated by a cytosolic serine-protease. Although L. guyanensis extracts are hemolytically inactive and unable to generate hemolytic activity, their membrane fraction becomes hemolytic in the presence of the cytosolic fraction of L. amazonensis, also by the action of a serine-protease. This suggests that L. guyanensis contains a potential lytic molecule, named here g-leishporin. The cytosolic fraction of L. guyanensis is unable to activate either a- or g-leishporin, indicating that this species does not possess the protease(s) that activate(s) the cytolysin. Trypsin, chymotrypsin, collagenase, Pronase and proteinase K, are also effective in activating a-leishporin but not g-leishporin. This suggests that the inactive forms of a-leishporin and g-leishporin are distinct in structure and/or are activated by different mechanisms. We are considering two hypotheses for the activation of leishporins: (1) proteolysis of an inactive precursor and (2) dissociation and/or proteolytic degradation of an inhibitory oligopeptide. The present data and preliminary results argue for the second hypothesis. We speculate that leishporin could be activated in the protease-rich, low pH, and dissociating environment of parasitophorous vacuole contributing for the release of the parasites from the macrophage.
Sujet(s)
Cytotoxines/métabolisme , Érythrocytes/physiologie , Hémolyse , Leishmania/métabolisme , Protéines de protozoaire/métabolisme , Serine endopeptidases/métabolisme , Animaux , Cytosol/métabolisme , Activation enzymatique , Humains , Concentration en ions d'hydrogène , Leishmania guyanensis/métabolisme , TempératureRÉSUMÉ
Pore-forming proteins (PFPs) may play important roles in pathogenesis by protozoan parasites by either directly damaging the plasma membrane of the host cells or ensuring intracellular survival of the parasites by promoting their exit from lysosomal vacuoles. The Leishmania amazonensis pore-forming cytolysin, leishporin, may play a crucial role in the pathogenesis of leishmaniasis.
Sujet(s)
Eucaryotes/pathogénicité , Porines/métabolisme , Protozooses/métabolisme , Protéines de protozoaire/métabolisme , Animaux , Membrane cellulaire/métabolisme , Interactions hôte-parasite , Humains , Lysosomes/métabolisme , Souris , Souris de lignée BALB CRÉSUMÉ
During their growth in vitro, promastigotes of Leishmania amazonensis undergo differentiation from complement-susceptible to complement-resistant forms. Here, we demonstrate that both forms bind comparable amounts of C3 on their surfaces, with the predominant molecule species being the haemolytically active C3b. Likewise, equivalent amounts of C9 are deposited on both forms of promastigotes. However, while C9-bearing complexes are exposed on the cell surface of resistant promastigotes, they are cryptic in the susceptible stage of the parasites. The membrane fraction of complement-resistant promastigote lysates has the ability to inhibit complement-mediated haemolysis, blocking C9, but not C3 deposition to complement-activating complexes. Moreover, the membrane fraction of complement-resistant promastigote lysates can inhibit the late steps of guinea-pig erythrocyte lysis much more efficiently than complement-susceptible ones. Our results indicate that L. amazonensis promastigotes evade complement killing by inhibiting the cytolytic pathway of the complement cascade.
Sujet(s)
Protéines du système du complément/immunologie , Leishmania mexicana/immunologie , Leishmania mexicana/pathogénicité , Animaux , Cycle cellulaire , Membrane cellulaire/immunologie , Complément C3/immunologie , Complément C3/métabolisme , Complément C3b/immunologie , Complément C3b/métabolisme , Complément C9/immunologie , Complément C9/métabolisme , Dosage de l'activité hémolytique du complément , Protéines inhibitrices du complément , Voie alterne d'activation du complément , Test ELISA , Cochons d'Inde , Interactions hôte-parasite , Humains , Leishmania mexicana/croissance et développementRÉSUMÉ
We describe here that parasites of the genus Leishmania contain a cytolytic activity which acts optimally at pH 5.0 to 5.5 and at 37 degrees C in vitro. or the four species examined, Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) major presented considerable hemolytic activity, whereas Leishmania (Viannia) panamensis and Leishmania (Viannia) guyanensis showed little and no hemolytic activity, respectively. The cytolytic factor of L. amazonensis promastigotes was characterized as a protein with no protease-, phospholipase-, or detergent-like activity, probably localized inside membranous vesicles. The use of osmotic protectants revealed the colloid-osmotic nature of hemolysis, which is indicative of pore formation in the membranes of target cells. This putative pore-forming protein also damaged nucleated cells, including macrophages, causing an increase in their membrane permeability with leakage of cytoplasmic proteins. Both promastigotes and amastigotes express this lytic activity, suggesting that the cytolysin may have a function in both stages of this parasite. The pH and temperature required for optimal activity indicate that it might be more effective within the mammalian host, particularly inside the macrophage parasitophorous vacuole. In promastigotes of L. amazonensis, the expression of lytic activity seems to be regulated during their growth in vitro, being maximal at the early stationary phase.
Sujet(s)
Cytotoxines/physiologie , Leishmaniose/immunologie , Protéines de protozoaire/physiologie , Animaux , Acide édétique/pharmacologie , Hémolyse , Humains , Concentration en ions d'hydrogène , Macrophages/physiologie , LapinsRÉSUMÉ
Two nuclear factors, designated NF-PI and NF-P2, have been shown to bind to an enhancer 9-base motif (5'-ACAGGAAGT-3', NF-P motif) present within the 5'-flanking region of the mouse perforin gene. Our previous studies have shown that, although NF-P1 and NF-P2 differ in cell-type distribution and molecular mass, with NF-P2 being killer-cell-specific and smaller, the two factors appear to share common DNA-binding subunit(s). We have postulated that the biochemical event involved in the induction of NF-P2 could be the dissociation of a non-DNA-binding subunit from NF-P1, rendering the newly formed NF-P2 transcriptionally active. By using a cell-free system in the present study, we have demonstrated that a variety of chemical agents capable of denaturing or dissociating protein complexes, including guanidinium/HCl, detergents (SDS plus Nonidet P-40) and high-salt solutions, could convert NF-P1 into NF-P2. Unlike in intact cells, where induction of NF-P2 is restricted to killer lymphocytes, this conversion occurred in nuclear extracts derived from both cytotoxic lymphocytes and non-cytotoxic cells. Although the mechanism that restricts the induction of NF-P2 to killer- lymphocytes in vivo remains unresolved, these results support the hypothetical 'dissociation' model for the generation of NF-P2. The results also imply that the absence of perforin expression in non-cytotoxic cells may be due to the suppression of the induction of the killer-cell-specific trans-acting factor NF-P2.
Sujet(s)
Extrait cellulaire/composition chimique , Éléments activateurs (génétique) , Cellules tueuses naturelles/composition chimique , Glycoprotéines membranaires/génétique , Protéines nucléaires/métabolisme , Lymphocytes T cytotoxiques/composition chimique , Animaux , Séquence nucléotidique , Régulation de l'expression des gènes , Glycoprotéines membranaires/métabolisme , Souris , Modèles biologiques , Données de séquences moléculaires , Masse moléculaire , Protéines nucléaires/composition chimique , Perforine , Perforines , Dénaturation des protéines , Spécificité du substrat , Lymphocytes T cytotoxiques/effets des médicaments et des substances chimiques , Régulation positiveRÉSUMÉ
Several organisms, including the protozoa Entamoeba histolytica and Trypanosoma cruzi, have been shown to contain pore-forming proteins (PFP) thought to play a role in the pathogenesis of the diseases they generate. In the present report, we show that promastigotes of Leishmania amazonensis express a hemolysin that appears to cause colloid-osmotic lysis, typical of pore formation. This hemolysin affects red blood cells of different species at 37 degrees C, but not at 0 degrees C, with maximum activity at pH 5.0. The hemolytic activity is heat-labile, but lysis is not affected by protease inhibitors. These results suggest the involvement of a protein with no proteolytic or detergent activity. Hemolysis is inhibited by polyethyleneglycol, suggesting its colloid-osmotic nature. Hemolytic extracts of the parasite contain a polypeptide that reacts with antibodies to perforin from mouse cytotoxic T lymphocytes or to C9 from human complement. In addition, genomic DNA of L. amazonensis contains a fragment that hybridizes to a perforin cDNA probe. The circumstantial evidence suggests that the L. amazonensis hemolytic activity may be mediated by a PFP homologous to perforin and C9.
Sujet(s)
Hémolysines/métabolisme , Hémolyse/physiologie , Peptides/métabolisme , Animaux , Concentration en ions d'hydrogène , Leishmania mexicana , Peptides/physiologieRÉSUMÉ
The gene encoding the cytolytic protein perforin is selectively expressed by activated killer lymphocytes. To understand the mechanisms underlying the cell-type-specific expression of this gene, we have characterized the regulatory functions and the DNA-protein interactions of the 5'-flanking region of the mouse perforin gene (Pfp). A region extending from residues +62 through -141, which possesses the essential promoter activity, and regions further upstream, which are able to either enhance or suppress gene expression, were identified. The region between residues -411 and -566 was chosen for further characterization, since it contains an enhancer-like activity. We have identified a 32-mer sequence (residues -491 to -522) which appeared to be capable of enhancing gene expression in a killer cell-specific manner. Within this segment, a 9-mer motif (5'-ACAGGAAGT-3', residues -505 to -497; designated NF-P motif), which is highly homologous to the Ets proto-oncoprotein-binding site, was found to interact with two proteins, NF-P1 and NF-P2. NF-P2 appears to be induced by reagents known to up-regulate the perforin message level and is present exclusively in killer cells. Electrophoretic mobility shift assay and UV cross-linking experiments revealed that NF-P1 and NF-P2 may possess common DNA-binding subunits. However, the larger native molecular mass of NF-P1 suggests that NF-P1 contains an additional non-DNA-binding subunit(s). In view of the homology between the NF-P motif and other Ets proto-oncoprotein-binding sites, it is postulated that NF-P1 and NF-P2 belong to the Ets protein family. Results obtained from the binding competition assay, nevertheless, suggest that NF-P1 and NF-P2 are related to but distinct from Ets proteins, e.g., Ets-1, Ets-2, and NF-AT/Elf-1, known to be expressed in T cells.
Sujet(s)
Cellules tueuses naturelles/physiologie , Glycoprotéines membranaires/génétique , Protéines proto-oncogènes/métabolisme , Séquences d'acides nucléiques régulatrices , Lymphocytes T cytotoxiques/physiologie , Facteurs de transcription/métabolisme , Animaux , Séquence nucléotidique , Sites de fixation , Lignée cellulaire , Chloramphenicol O-acetyltransferase/métabolisme , Protéines de liaison à l'ADN/isolement et purification , Protéines de liaison à l'ADN/métabolisme , Humains , Interleukine-2/pharmacologie , Cellules LAK/effets des médicaments et des substances chimiques , Cellules LAK/physiologie , Cellules tueuses naturelles/effets des médicaments et des substances chimiques , Cellules tueuses naturelles/immunologie , Leucémie à cellules T , Activation des lymphocytes , Sarcome à mastocytes , Souris , Souris de lignée C57BL , Données de séquences moléculaires , Masse moléculaire , Oligodésoxyribonucléotides , Perforine , Perforines , Protéine proto-oncogène c-ets-1 , Protéines proto-oncogènes c-ets , Protéines recombinantes/pharmacologie , Lymphocytes T cytotoxiques/effets des médicaments et des substances chimiques , Lymphocytes T cytotoxiques/immunologie , 12-Myristate-13-acétate de phorbol/pharmacologie , Thymome , Tumeurs du thymus , Transfection , Cellules cancéreuses en cultureRÉSUMÉ
Schistosomula of Schistosoma mansoni became resistant to antibody-dependent complement damage in vitro after pre-incubation with normal human erythrocytes (NHuE) whatever the ABO or Rh blood group. Resistant parasites were shown to acquire host decay accelerating factor (DAF), a 70 kDa glycoprotein attached to the membrane of NHuE by a GPI anchor. IgG2a mAb anti-human DAF (IA10) immunoprecipitated a 70 kDa molecule from 125I-labeled schistosomula pre-incubated with NHuE and inhibited their resistance to complement-dependent killing in vitro. Incubation of schistosomula with erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNHE) or SRBC, which are DAF-deficient, did not protect the parasites from complement lesion. Supernatant of 100,000 x g collected from NHuE incubated for 24 h in defined medium was shown to contain a soluble form of DAF and to protect schistosomula from complement killing. Schistosomula treated with trypsin before incubation with NHuE ghosts did not become resistant to complement damage. On the other hand, pre-treatment with chymotrypsin did not interfere with the acquisition of resistance by the schistosomula. These results indicate that, in vitro, NHuE DAF can be transferred to schistosomula in a soluble form and that the binding of this molecule to the parasite surface is dependent upon trypsin-sensitive chymotrypsin-insensitive polypeptide(s) present on the surface of the worm.
Sujet(s)
Protéines du système du complément/immunologie , Schistosoma mansoni/physiologie , Animaux , Antigènes CD/métabolisme , Antigènes CD55 , Chymotrypsine/pharmacologie , Protéines inhibitrices du complément/déficit , Protéines inhibitrices du complément/métabolisme , Milieux de culture/pharmacologie , Érythrocytes/parasitologie , Cochons d'Inde , Protéines d'helminthes/métabolisme , Hémoglobinurie paroxystique/immunologie , Hémoglobinurie paroxystique/parasitologie , Larve , Glycoprotéines membranaires/métabolisme , Modèles biologiques , Peptides/métabolisme , Liaison aux protéines , Schistosoma mansoni/effets des médicaments et des substances chimiques , Schistosoma mansoni/croissance et développement , Schistosomiase à Schistosoma mansoni/immunologie , Schistosomiase à Schistosoma mansoni/parasitologie , Ovis , Trypsine/pharmacologieRÉSUMÉ
Decay-accelerating factor (DAF) is a 70-kD membrane glycoprotein that prevents complement (C)-mediated hemolysis by blocking the assembly or accelerating the decay of C3 convertase. Purified DAF is known to incorporate into the membrane of DAF-deficient cells, inhibiting lysis. Since Schistosoma mansoni is a blood-dwelling parasite, we investigated whether DAF can be transferred from human erythrocytes to the worm and protect it against C-mediated killing in vitro. We have found that schistosomula (schla) incubated with normal human erythrocytes (N-HuE), but not with DAF-deficient erythrocytes, become resistant to C damage in vitro. Protected parasites acquire a 70-kD surface protein which can be immunoprecipitated by anti-DAF antibodies. The acquired resistance is abrogated by treatment of N-HuE-incubated parasites with anti-DAF antibody. These results indicate that, in vitro, N-HuE DAF can be transferred to schla, and suggest its participation in preventing their C-mediated killing. This could represent an important strategy of parasites to evade the host's immune response in vivo.
Sujet(s)
Protéines du sang/physiologie , Protéines inhibitrices du complément/physiologie , Protéines du système du complément/immunologie , Protéines membranaires/physiologie , Schistosoma mansoni/immunologie , Animaux , Protéines du sang/analyse , Protéines du sang/déficit , Antigènes CD55 , Cellules cultivées , Érythrocytes/immunologie , Humains , Immunoglobuline G/immunologie , Protéines membranaires/analyse , Protéines membranaires/déficit , Pronase/pharmacologie , Lapins , Trypsine/pharmacologieRÉSUMÉ
Schistosoma mansoni infected hosts produce an IgG that mediates the complement-dependent killing of schistosomula in vitro. In this study, we followed the levels of serum lethal antibody during infection of rats and mice. Rats presented detectable lethal activity early in the course of infection with a peak in the 6-8th week of infection. This activity declined to non-detectable levels within 2 weeks, remaining low up to the 20-26th week. In mice, lethal antibody was not detected before 7-12 weeks of infection, but raised to higher levels, as compared to non-infected animals, up to 20-24 weeks after infection. We correlate lethal antibody and protective immunity suggesting that the antibody-mediated complement-dependent cytotoxicity to schistosomula play a role in the immunity to reinfection.
Sujet(s)
Anticorps antihelminthe/biosynthèse , Immunoglobuline G/biosynthèse , Schistosoma mansoni/immunologie , Schistosomiase à Schistosoma mansoni/immunologie , Animaux , Anticorps antihelminthe/immunologie , Tolérance immunitaire , Immunoglobuline G/immunologie , Larve , Souris , Rats , Schistosoma mansoni/croissance et développementRÉSUMÉ
Schistosomula of Schistosoma mansoni are known to be killed in vitro by complement and IgG (lethal antibody). To investigate whether this mechanism reflects the in vivo situation, we isolated IgG subclasses from sera of infected rats and assayed their ability to promote the complement-mediated killing of schistosomula in vitro as well as to protect normal recipients from a challenge infection. We found that a serum fraction containing only IgG2a + IgG2b has lethal activity to schistosomula in vitro, whereas a fraction containing only IgG1 + IgG2c fails to kill schistosomula in the presence of complement. The assay of protective activity has shown that the same fraction containing the lethal activity (IgG2a + IgG2b) was able to reduce the number of schistosomula recovered from lungs. These results provide evidence of the participation of IgG2a and/or IgG2b, but not IgG1 or IgG2c, in protective immunity to S. mansoni in rats, possibly through a complement-mediated mechanism.