RESUMEN
Host responses to the transmittable stages of the malaria parasite may reduce transmission effectively. Transmission-reducing activity (TRA) of human serum can be determined as a percentage, using the Standard Membrane Feeding Assay (SMFA). This laboratory assay was evaluated using the results of 121 experiments with malaria-endemic sera among which many repeated measurements were obtained. The assay consists of the feeding of Anopheles stephensi mosquitoes with cultured Plasmodium falciparum gametocytes, mixed with human red blood cells, and control and experimental sera. The TRA of individual sera was determined by the comparison of oocyst densities between these sera. Bootstrap data on oocyst densities in individual mosquitoes in control feeds were used to construct confidence limits for TRA percentages of serum feeds. Low (<20%) and high TRA (>90%) values for individual sera were usually reproduced in a second experiment, whereas this was more difficult for values between 20% and 90%. The observed variability of TRA values is explained in part by the variability in oocyst density per mosquito. Oocyst densities in control feeds varied more between experiments than within experiments and showed a slight decline over the 3 years of experiments. Reproducibility of TRA of field sera was low (20%) between experiments, but much higher (61 %) within experiments. A minimum of 35 oocysts per mosquito in control feeds gave optimal reproducibility (44%) between experiments. We recommend that (1) sera are compared within an experiment, or (2) assays are only analysed where controls have at least 35 oocysts per mosquito. The SMFA is under the recommended conditions appropriate for the study of factors that may influence TRA, e.g. transmission blocking vaccines.
Asunto(s)
Anopheles/parasitología , Conducta Alimentaria/fisiología , Malaria Falciparum/sangre , Malaria Falciparum/transmisión , Membranas Artificiales , Animales , Anopheles/fisiología , Simulación por Computador , Humanos , Insectos Vectores , Malaria Falciparum/prevención & control , Modelos Biológicos , Oocistos , Plasmodium falciparum/crecimiento & desarrollo , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
Release of soluble Granzymes (sGranzymes) is considered to reflect activation of cytotoxic T lymphocytes and NK cells. sGranzymes and a number of pro-inflammatory cytokines were measured in plasma of malaria patients with natural or experimentally induced Plasmodium falciparum infections. Concentrations of sGranzyme A and B, IL-10, IL-12p70 and CRP were significantly increased in African children presenting with clinical malaria; IL-10 and CRP concentrations were significantly correlated with disease severity. In nonimmune Dutch volunteers which were experimentally infected by P. falciparum-infected mosquitoes, sGranzyme A increment started 1-2 days prior to clinical symptoms and microscopically detectable parasitaemia. This coincided with increases in IFNgamma, IL-12p40 and IL-8, while sGranzyme B and IL-10 levels increased 24-48 h later. The elevation of sGranzyme A and IFNgamma in nonimmune volunteers suggests that NK cells are activated upon release of parasites by infected liver cells and subsequently during blood stage infection; thus, NK cells are likely involved innate immune human host resistance in the early phase of a malaria infection.
Asunto(s)
Malaria Falciparum/enzimología , Serina Endopeptidasas/sangre , Adolescente , Proteína C-Reactiva/análisis , Niño , Preescolar , Granzimas , Humanos , Lactante , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-12/sangre , Células Asesinas Naturales/inmunología , Malaria Falciparum/inmunología , Parasitemia/enzimología , Parasitemia/inmunología , Solubilidad , Linfocitos T Citotóxicos/inmunologíaAsunto(s)
Antígenos de Protozoos/inmunología , Plasmodium/inmunología , Animales , Anopheles/parasitología , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/biosíntesis , Antígenos de Protozoos/química , Femenino , Humanos , Insectos Vectores/parasitología , Malaria/sangre , Malaria/inmunología , Malaria/parasitología , Masculino , Parasitemia/parasitología , Plasmodium/crecimiento & desarrollo , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium falciparum/inmunología , Plasmodium vivax/crecimiento & desarrollo , Plasmodium vivax/inmunología , Estructura Terciaria de Proteína , Proteínas Protozoarias/biosíntesis , Proteínas Protozoarias/química , Proteínas Protozoarias/inmunología , Glándulas Salivales/parasitología , Diferenciación SexualAsunto(s)
ADN Protozoario/sangre , Malaria Falciparum/parasitología , Parasitemia/parasitología , Plasmodium falciparum/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Animales , Culicidae/parasitología , Culicidae/fisiología , Conducta Alimentaria , Humanos , Plasmodium falciparum/genética , Sensibilidad y EspecificidadRESUMEN
We report the first construction of two combinatorial human phage display libraries derived from malaria-immune patients. Specific single-chain Fv fragments (scFv) against Pfs48/45, a gamete surface protein of the sexual stages of Plasmodium falciparum, were selected and analyzed extensively. The selected scFv reacted with the surface of extracellular sexual forms of the parasite and showed Pfs48/45 reactivity on immunoblot. The scFv inhibit binding of human malaria sera to native Pfs48/45 from gametocytes. Moreover, the scFv bind to target epitopes of Pfs48/45 exposed in natural infections. Sequence analysis of eight scFv clones specific for epitope III of Pfs48/45 revealed that these clones could be divided into one V(H) family-derived germ-line gene (V(H)1) and two V(L) family segments (V(L)2 and V(K)I).
Asunto(s)
Anticuerpos/inmunología , Glicoproteínas de Membrana/inmunología , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos/química , Anticuerpos/genética , Bacteriófagos/genética , Epítopos/inmunología , Humanos , Glicoproteínas de Membrana/química , Datos de Secuencia Molecular , Proteínas Protozoarias/química , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Homología de Secuencia de AminoácidoAsunto(s)
Miosinas/metabolismo , Plasmodium berghei/crecimiento & desarrollo , Plasmodium berghei/metabolismo , Secuencia de Aminoácidos , Animales , Estadios del Ciclo de Vida , Datos de Secuencia Molecular , Miosinas/química , Miosinas/genética , Plasmodium berghei/genética , Plasmodium berghei/patogenicidad , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Análisis de Secuencia de ADNRESUMEN
Immunotoxins (ITs) may be very potent to erradicate tumour growth in vivo. We investigated the influence of the IT-dose, in relation to the establishment of the tumour, on the anti-tumour activity of CD22-recombinant (rec) ricin A for a disseminated tumour (Ramos) in SCID mice. Furthermore, the enhancement of the IT cytotoxicity in vivo by chloroquine was assessed. CD22-rec ricin A appeared to be highly effective. Paralysis of the hind legs was significantly delayed by a very low IT-dose of 2 microg administered intravenously (i.v.) 7 days after i.v. inoculation of the tumour cells. Even a dose of 30 microg administered 21 days after inoculation of the target cells significantly delayed the onset of paralysis up to 8 days compared with the median paralysis time (MPT) of the control group. The efficacy of treatment was obviously influenced by the establishment of the tumour, the tumour load and localisation. The anti-tumour activity of 10 and 30 microg IT diminished when the IT was administered after increasing the time lag following inoculation of tumour cells. Delaying IT administration resulted in growth of solid tumours. This implies that cells migrate to sanctuaries protected from the IT indicating that the anti-tumour activity was influenced by the accessibility of the IT to the target cells. The in vivo anti-tumour activity of CD22-rec ricin A could not be enhanced by simultaneously administered chloroquine, despite the continuous infusion with an intraperitoneally (i.p.) implanted mini-osmotic pump. Ex vivo experiments revealed that the maximally tolerated serum concentration (3.9 microM) was too low to be effective. In conclusion, CD22-rec ricin A is highly effective for in vivo treatment of B-cell malignancies, in particular if treatment is started when the tumour load is low and before migration takes place to poorly accessible sanctuaries.
Asunto(s)
Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos B/inmunología , Linfoma de Burkitt/tratamiento farmacológico , Moléculas de Adhesión Celular , Modelos Animales de Enfermedad , Inmunotoxinas/administración & dosificación , Lectinas , Ratones SCID , Animales , Antineoplásicos/farmacología , Linfoma de Burkitt/patología , Cloroquina/administración & dosificación , Cloroquina/farmacología , Cloroquina/toxicidad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Humanos , Inmunotoxinas/uso terapéutico , Ratones , Trasplante de Neoplasias , Ricina/farmacología , Lectina 2 Similar a Ig de Unión al Ácido Siálico , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/trasplanteRESUMEN
Infections with certain species of Plasmodium and Babesia induce, among other symptoms, cerebral pathology. The finding of heavily parasitized cerebral capillaries upon postmortem examination has led to the assumption that blockage of capillaries with infected red blood cells caused the cerebral symptoms and subsequent death. As this type of cerebrovascular pathology is found both in humans dying from malaria and in cattle dying from babesiosis, the latter could possibly be used as an animal model for the study of human cerebral malaria. However, before such a model system is adopted, the experimental data concerning cerebral pathology of babesiosis needs critical evaluation. Here, Theo Schetters and Wijnand Eling review the pathological mechanisms in cerebral babesiosis and relate these to cerebral malaria. Finally, they discuss the use of animal model systems for specific aspects of the pathological picture.
Asunto(s)
Babesia bovis/patogenicidad , Babesiosis/patología , Modelos Animales de Enfermedad , Malaria Cerebral/patología , Animales , Babesiosis/fisiopatología , Bovinos , Humanos , Malaria Cerebral/fisiopatología , Ratones , Microcirculación/parasitología , Bazo/parasitologíaRESUMEN
The introduction of reactive thiol groups in recombinant human tumor necrosis factor (TNF) alpha (rhTNF-alpha) by the reagent succinimidyl-S-acetylthioacetate resulted in the formation of a chemically stabilized rhTNF-alpha trimer (rhTNFalpha-AT; as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis). rhTNFalpha-AT showed a substantially enhanced protective efficacy against the development of experimental murine cerebral malaria (ECM) after intravenous injection compared to the protective efficacy of nonmodified rhTNF-alpha. Administration of thiolated rhTNF-alpha with protected thiol groups (rhTNFalpha-ATA; no stabilized trimers in vitro) exhibited the same protective efficacy against ECM, while in vitro bioactivity was reduced. Parasitemia was significantly suppressed in rhTNF-treated mice that were protected against ECM but not in treated mice that developed ECM. Protection against ECM was not related to increased concentrations in plasma of soluble TNF receptor 1 and 2 directly after injection or at the moment of development of ECM in nontreated mice. The results indicate that thiolation of rhTNF-alpha leads to the formation of stable trimers with increased potential in vivo.
Asunto(s)
Malaria Cerebral/prevención & control , Plasmodium berghei , Factor de Necrosis Tumoral alfa/administración & dosificación , Animales , Humanos , Inyecciones Intravenosas , Malaria Cerebral/sangre , Ratones , Receptores del Factor de Necrosis Tumoral/sangre , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/química , Succinimidas , Reactivos de Sulfhidrilo , Sulfuros , Factor de Necrosis Tumoral alfa/químicaRESUMEN
The present study shows that treatment with recombinant human tumour necrosis factor-alpha (rhTNF-alpha) can suppress parasitaemia and prevents development of experimental cerebral malaria (ECM) in Plasmodium berghei K173-infected mice. Mice received rhTNF-alpha treatment either by subcutaneous injection of free or liposome-encapsulated rhTNF-alpha or sustained intraperitoneal administration of rhTNF-alpha given via mini-osmotic pumps. Low-dose treatment with a subcutaneous bolus injection of rhTNF-alpha protected against ECM when treatment was started on day 5 or 6 after infection. The same protective efficacy was obtained either by subcutaneous injection of liposome-encapsulated rhTNF-alpha or by sustained release from osmotic pumps, but in the latter case a 10-fold lower daily dose of rhTNF-alpha was sufficient. Treatment with rhTNF-alpha substantially suppressed parasitaemia in ECM-protected mice, but not in mice developing ECM. Thus, the rhTNF-alpha mediated suppression of parasitaemia is directly or indirectly involved in protection against ECM. Sustained delivery of rhTNF-alpha through osmotic pumps, but not by subcutaneous injection of liposome-encapsulated rhTNF-alpha, resulted in increased concentrations of soluble mouse TNF receptor R75 (sTNFR75) in plasma at day 9 after infection when non-treated mice die of ECM. Thus, protection against ECM is not directly correlated with the sTNFR75 concentrations at day 9 after infection.
Asunto(s)
Malaria Cerebral/terapia , Parasitemia/tratamiento farmacológico , Plasmodium berghei , Factor de Necrosis Tumoral alfa/uso terapéutico , Administración Cutánea , Animales , Antígenos CD/sangre , Portadores de Fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Bombas de Infusión , Liposomas , Malaria Cerebral/parasitología , Ratones , Ratones Endogámicos C57BL , Receptores del Factor de Necrosis Tumoral/sangre , Receptores Tipo II del Factor de Necrosis Tumoral , Proteínas Recombinantes/uso terapéutico , Organismos Libres de Patógenos Específicos , Factores de TiempoRESUMEN
Our study describes liposomes (conventional or sterically stabilized) as carrier systems for recombinant human tumor necrosis factor-alpha (rhTNF-alpha) to increase its protective efficacy against Plasmodium berghei-induced experimental cerebral malaria (ECM) in mice. rhTNF-alpha was either covalently coupled to the outer surface of preformed liposomes or encapsulated into the liposomes. For coupling to the liposomes, reactive thiol groups were introduced in rhTNF-alpha by reaction with N-succinimidyl S-acetylthioacetate. Intravenous injection of liposome-bound rhTNF-alpha substantially enhanced protection against ECM as compared with injection of free rhTNF-alpha. A similar protective efficacy against ECM was obtained by treatment with rhTNF-alpha coupled to either conventional or sterically stabilized liposomes. Encapsulation of rhTNF-alpha into liposomes did not improve the protective efficacy of rhTNF-alpha against P. berghei-induced ECM. Parasitemia was suppressed by treatment with either free or liposome-bound rhTNF-alpha in mice protected against ECM, but not in rhTNF-alpha-treated mice developing ECM. These data suggest that the effect of rhTNF-alpha on parasitemia plays a role in establishing protection against ECM. Our studies indicate that liposome-bound rhTNF-alpha exhibits an enhanced protective efficacy against ECM compared with free rhTNF-alpha. It is hypothesized that thiolation of rhTNF-alpha and coupling to the liposomal bilayer stabilizes the bioactive trimeric configuration of rhTNF-alpha.
Asunto(s)
Antimaláricos/administración & dosificación , Malaria Cerebral/prevención & control , Parasitemia/prevención & control , Plasmodium berghei , Factor de Necrosis Tumoral alfa/administración & dosificación , Animales , Antimaláricos/uso terapéutico , Modelos Animales de Enfermedad , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Inyecciones Intravenosas , Liposomas , Malaria Cerebral/etiología , Ratones , Ratones Endogámicos C57BL , Plasmodium berghei/efectos de los fármacos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
Experimental cerebral malaria (ECM) can be induced in C57B1 mice by infection with Plasmodium berghei K173 parasites. Behavioral changes shortly before they die of ECM may reflect disturbance of the integrity of the blood-brain barrier (BBB). Folic acid elicits strong convulsive activity if the permeability of the BBB is increased. Administration of folic acid to mice during development of ECM induced convulsions. Interventions known to prevent fatal outcome from ECM, such as splenectomy or treatment with anti-CD4 or anti-CD8 monoclonal antibodies, also prevented sensitivity to folic acid-induced convulsions. In addition, infected mice with ECM and sensitive to folic acid-induced convulsions, recovered from this sensitivity after treatment with anti-T cell antibodies within 4 h. These data suggest that disturbance of the permeability of the BBB can be reversed and depends on the involvement of T cells.
Asunto(s)
Barrera Hematoencefálica , Malaria Cerebral/inmunología , Convulsiones/prevención & control , Esplenectomía , Linfocitos T/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Ácido Fólico/farmacología , Ratones , Ratones Endogámicos C57BL , Convulsiones/inducido químicamenteRESUMEN
A precondition for the development of a transmission blocking vaccine based on the sexual stage-specific surface antigen Pfs48/45 of Plasmodium falciparum is its heterologous synthesis in a native state. Here we describe the production of recombinant Pfs48/45 in Escherichia coli. Two recombinant proteins, of which one is a glutathione-S-transferase fusion protein, were produced. Enzyme-linked immunosorbent assays showed that at least a subfraction of the recombinant proteins had a conformation capable of binding transmission blocking monoclonal antibodies. However, despite the fact that both proteins were very immunogenic, they did not induce transmission blocking immunity in mice or rabbits. Immunological studies with congenic mouse strains demonstrated that immune responses could be boosted with gametocyte extracts and were not restricted to a particular class II major histocompatibility complex haplotype.
Asunto(s)
Vacunas contra la Malaria/inmunología , Malaria Falciparum/inmunología , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , Proteínas Recombinantes de Fusión/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antiprotozoarios/sangre , Especificidad de Anticuerpos , Escherichia coli , Vectores Genéticos , Humanos , Ratones , Ratones Congénicos , ConejosRESUMEN
Young male Wistar rats were fed a purified, vegetable, low-protein diet containing 6% protein from maize gluten and 2% from soy protein isolate, or comparable diets in which maize gluten was replaced partly or completely by the equivalent amount of a milk protein concentrate. Diets with adequate protein level (16% or 22%) served as a control. At 21 or 31 days of age, the rats were infected with 3000 or 100000 erythrocytes parasitized with Plasmodium berghei. Results reported include body weight, mortality, paralysis and parasitaemia. Dietary replacement of part of the maize gluten protein by milk protein increased weight gain, but aggravated the malaria, as shown by increases in parasitaemia, paralysis and mortality. The aggravating effect of milk protein was dose-dependent. With only 4% milk protein in an 8% total protein diet, the disease symptoms were nearly as severe as with diets adequate in protein level. With a vegetable-only 8% protein diet symptoms were considerably less severe.
Asunto(s)
Malaria/veterinaria , Proteínas de la Leche/administración & dosificación , Proteínas de Vegetales Comestibles/administración & dosificación , Plasmodium berghei , Enfermedades de los Roedores/etiología , Animales , Relación Dosis-Respuesta a Droga , Inmunidad Innata , Malaria/etiología , Malaria/inmunología , Masculino , Parasitemia/etiología , Parasitemia/inmunología , Parasitemia/veterinaria , Ratas , Ratas Wistar , Enfermedades de los Roedores/inmunología , Factores de Tiempo , Destete , Aumento de PesoRESUMEN
Optimization of desferrioxamine B (DFO) delivery for the treatment of malaria was studied in Plasmodium vinckei infected mice. DFO was administered by three different treatment regimens: (1) multiple subcutaneous injections of free DFO, (2) intraperitoneal infusion of free DFO, or (3) multiple subcutaneous injections of liposomal DFO. In a first series of experiments, DFO treatment was started prior to infection. Multiple subcutaneous injections of free DFO before and during infection suppressed parasitemia, whereas injections only prior to infection did not. Suppression of parasitemia and long-term survival (>1 month after infection) of mice were obtained by intraperitoneal infusion starting 1 day before infection (14 days, 130 mg DFO/kg/day) or by subcutaneous injections of liposomal DFO prior to infection (days -1 and 0, 400 or 800 mg DFO/kg/day). The efficacy of the antimalarial activity of liposomal DFO was influenced by the drug-to-lipid ratio but was hardly affected by bilayer rigidity. In a second series of experiments, DFO treatment was started at days 6 and 7 after infection. Parasitemia was reduced by all three treatment regimens; however, long-term survival was obtained only by treatment with liposomal DFO (days 7 and 8, 400 mg/kg/day). The present results indicate that continuous exposure of the parasite to low doses of DFO suffice to clear parasitemia, whereas high doses of free DFO administered intermittently do not. A right balance between dose of DFO, time of exposure to DFO, and parasitemia suppresses parasitemia even in the treatment of late-stage malaria. It was shown that liposomes are suitable carrier systems for DFO in experimental malaria therapy when given prior to infection and, moreover, in the treatment of advanced stages of malaria.
Asunto(s)
Deferoxamina/administración & dosificación , Sistemas de Liberación de Medicamentos , Quelantes del Hierro/administración & dosificación , Malaria/tratamiento farmacológico , Parasitemia/tratamiento farmacológico , Animales , Deferoxamina/uso terapéutico , Preparaciones de Acción Retardada , Portadores de Fármacos , Femenino , Infusiones Parenterales , Inyecciones Subcutáneas , Quelantes del Hierro/uso terapéutico , Liposomas , Ratones , Ratones Endogámicos C57BL , Organismos Libres de Patógenos Específicos , SobrevivientesAsunto(s)
Regulación del Desarrollo de la Expresión Génica , Fosfoproteínas/genética , Plasmodium falciparum/genética , ARN Ribosómico/genética , Proteínas Ribosómicas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Cartilla de ADN/química , ADN Protozoario/química , ADN Ribosómico/química , Biblioteca de Genes , Humanos , Datos de Secuencia Molecular , Fosfoproteínas/biosíntesis , Fosfoproteínas/química , Plasmodium falciparum/metabolismo , ARN Protozoario/química , ARN Protozoario/genética , ARN Ribosómico/química , Proteínas Ribosómicas/biosíntesis , Proteínas Ribosómicas/química , Alineación de Secuencia , Homología de Secuencia de AminoácidoRESUMEN
The present paper reports on the influence of the route of administration and liposome stability on the protective effect of liposome encapsulation of two model antitumor agents, mitoxantrone and doxorubicin. The results demonstrate that liposome encapsulation can protect surrounding tissue from the cytotoxic effects of the drugs after subcutaneous (s.c.) and intramuscular (i.m.) administration. The route of administration is an important factor influencing tissue damage. Liposomal mitoxantrone caused much less tissue irritation after im injection than after s.c. injection. Liposome stability is also an important factor. Liposomes composed of 'fluid-state' phospholipids only delayed the damaging effects of doxorubicin when injected sc. Liposomes with a more rigid nature were much more effective in preventing local tissue damage over a longer period of time when administered sc. Results suggest that slow release of liposome-associated drugs may eventually cause severe local tissue damage. The incorporation of the hydrophilic lipid derivative distearoylphosphatidylethanolamine-poly(ethyleneglycol) (PEG-PE) had no apparent effect on the protective effect of liposomes after sc administration.
Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Antineoplásicos Alquilantes/efectos adversos , Doxorrubicina/efectos adversos , Mitoxantrona/efectos adversos , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Doxorrubicina/administración & dosificación , Portadores de Fármacos , Femenino , Membrana Dobles de Lípidos , Liposomas , Ratones , Ratones Endogámicos C57BL , Mitoxantrona/administración & dosificación , Fosfatidiletanolaminas , PolietilenglicolesAsunto(s)
Malaria/parasitología , Parasitemia/parasitología , Plasmodium berghei/aislamiento & purificación , Animales , Anopheles , Antiinfecciosos/uso terapéutico , Femenino , Insectos Vectores , Malaria/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Parasitemia/tratamiento farmacológico , Sulfadiazina/uso terapéuticoRESUMEN
Unlike most other indigenous bacteria, segmented filamentous bacteria (SFB) are potent activators of the mucosal immune system. SFB are strongly anchored to the epithelial cells of the small intestine where they have a preference for mucosal lymphoid epithelium. Since SFB are only present in high numbers shortly after weaning, it was investigated whether an SFB-induced immune reaction results in the removal of these bacteria from the small intestine. A correlation was found between age and colonization levels in the small intestines of SFB monoassociated Swiss mice. Five-week-old athymic BALB/c (nu/nu) mice showed lower colonization levels than their heterozygous littermates, but the opposite was found at the age of 12 weeks. However, SFB inoculation of germfree Swiss mice resulted in higher colonization levels in 5-week-old mice when compared with 4-month-old mice. We conclude that SFB colonization levels in the small intestine are likely influenced by the activity of the mucosal immune system. However, an additional age-dependent factor that modulates SFB colonization levels cannot be excluded.
Asunto(s)
Bacterias/inmunología , Mucosa Intestinal/inmunología , Intestino Delgado/inmunología , Ganglios Linfáticos Agregados/microbiología , Factores de Edad , Animales , Bacterias/ultraestructura , Vida Libre de Gérmenes , Huésped Inmunocomprometido , Inmunoglobulina A/análisis , Mucosa Intestinal/microbiología , Mucosa Intestinal/ultraestructura , Intestino Delgado/microbiología , Intestino Delgado/ultraestructura , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Electrónica de RastreoRESUMEN
Mosquitoes are infected with Plasmodium falciparum by taking a blood meal from a gametocyte carrier. Since a mosquito takes a volume of 1 to 2 microl, a blood meal may contain 1 x 10(4) to 3 x 10(4) leukocytes (WBC). The majority of WBC are composed of neutrophils which may phagocytose and kill developing gametes inside the mosquito midgut. Phagocytosis was measured in vitro by a luminol-dependent chemiluminescence (CL) assay. In the presence of P. falciparum gametes, sera from areas of endemicity had an increased CL response compared to controls. In mosquito membrane feeding experiments some such sera showed a transmission reduction which was related to the presence of viable WBC. The results of this study suggest that phagocytosis of opsonized gametes inside the mosquito midgut occurs and can contribute to a reduction in the transmission of P. falciparum parasites.