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PubMed1985

Patterns of resistance of inbred mice to Trypanosoma cruzi are determined by parasite strain.

Host response and parasite behavior of three different T. cruzi strains (I-Peruvian, II-21SF, III-Colombian) were investigated by evaluating the course of infection in six inbred strains of mice (A/J, AKR, C3H/He, BALB/c, C57BL/10, DBA/1). Resistance was evaluated in terms of the harmonic mean survival time and the infection was monitored by parasitemia, histopathology and immunological parameters (immunoglobulin subclass levels and antibody titers). All six mouse strains showed high susceptibility to the Peruvian strain (Type I). However, they displayed a different spectrum of susceptibility to Types II and III. Each T. cruzi strain maintained its basic features in the different mouse strains. Despite different maximum levels, the parasitemic curves were characteristic for each type of T. cruzi strain. There was a correlation between the degree of resistance of strains DBA and B10 and their high levels of IgG2a and IgG2b, as well as the presence of the H-2d haplotype, indicating that the genetic background of the mice is also important. The inflammatory process varied with each mouse strain and was correlated with the levels of IgG2a, with resistant mice showing predominance of neutrophilic infiltration with a rise in IgG2a. The susceptible strains responded with a mild inflammatory process with predominance of mononuclear cells. These data suggest that the parasite strain is the most important factor determining the resistance of the different mouse strains to infection with T. cruzi.

Animals↗
PubMed1996

Susceptibility to Leishmania major in IL-4 transgenic mice is not correlated with the lack of a Th1 immune response.

IL-4 transgenic mice of C3H genetic background expressing IL-4 under the control of an MHC class I promoter were infected with Leishmania major and the immune response was assessed. In contrast to littermate control mice, the transgenic mice were unable to restrict the growth of the parasites as shown by the strong increase in footpad swelling and parasite numbers in the spleen. The observed susceptibility was markedly less severe than that observed in BALB/c mice. Restimulation of lymph node cells with L. major antigen in vitro and subsequent analysis of cytokine secretion revealed that, in contrast to BALB/c mice, the cells from the IL-4 transgenic mice secreted more IL-5 and similar amounts of IFN-gamma as did the cells from litter mate control mice. These results demonstrate that the transgenic expression of IL-4 in vivo leads to the generation of more Th2 cells without affecting the generation of IFN-gamma-producing Th1 cells. This indicates that under certain conditions Th1 and Th2 immune responses during infection with L. major are not mutually exclusive, and that other factors besides the secretion of IL-4 determine whether only a Th1 or a Th2 immune response develops. The observed susceptibility of IL-4 transgenic mice to L major was not due to the lack of IFN-gamma production but presumably to the transgenic and Th2 cell-derived IL-4 counteracting the otherwise protective effect of IFN-gamma on infected macrophages. Our results might help explain why humans develop cutaneous leishmaniasis even though IFN-gamma-producing cells are readily detectable in the lesions.

Animals↗
PubMed1990

Dependence on cell-mediated mechanisms for the appearance of crisis forms during Plasmodium chabaudi AS infection in C57BL/6 mice.

The appearance of crisis forms or degenerate, intraerythrocytic parasites in the peripheral blood of C57BL/6 hosts during the course of Plasmodium chabaudi AS infection was analysed. Following intraperitoneal injection with 10(6) parasitized erythrocytes, C57BL/6 hosts, which are resistant to this species of rodent Plasmodium, eliminate the parasite from the peripheral blood by 4 weeks and recover from acute infection. Elimination of the parasite coincides with the appearance in the peripheral blood of almost all the parasites as crisis forms. A role for cell-mediated immunity in the induction of crisis forms of Plasmodium species has previously been suggested. To define the role of cell-mediated immunity in the appearance of intraerythrocytic crisis forms in the peripheral blood during acute malaria, the outcome of P. chabaudi AS infection, the course of parasitemia and the appearance of crisis forms in mice with either genetically determined or experimentally induced immunodeficiencies on the resistant C57BL-derived background were examined. The mice used were either B-cell deficient (mu-suppressed from birth). T-cell deficient (nu/nu mice), C5 deficient or splenectomized prior to infection. The appearance of intraerythrocytic crisis forms in the peripheral blood during the course of P. chabaudi AS infection is shown to be dependent on cell-mediated mechanisms which require the presence of T cells as well as an intact spleen for the most efficient elimination of this parasite.

Animals↗
PubMed1999

Plasmodium falciparum mdr1 mutations and in vivo chloroquine resistance in Indonesia.

Mutations in the Pfmdr1 gene are reported to be associated with chloroquine resistance in some Plasmodium falciparum isolates. A polymerase chain reaction/restriction fragment length polymorphism method was used for the detection of Pfmdr1 mutations in chloroquine-resistant field isolates of P. falciparum collected in Irian Jaya. The frequency of Pfmdr1 mutations was significantly higher in chloroquine-resistant P. falciparum parasites than background frequencies observed in the same location. The 7G8 mutation was identified in some parasites although always in a mixed genotype status. Chloroquine-resistant P. falciparum specimens were characterized using the World Health Organization 28-day criteria, supplemented by demonstrating adequate chloroquine absorption and genetic analysis.

ATP-Binding Cassette Transporters↗
PubMed1985

Immunity to leprosy. II. Genetic control of murine T cell proliferative responses to Mycobacterium leprae.

T cell proliferative responses to Mycobacterium leprae were measured after immunization of mice at the base of the tail with antigen and challenging lymphocytes from draining lymph nodes in culture with M. leprae. This T cell response to M. leprae has been compared in 18 inbred strains of mice. C57BL/10J mice were identified as low responder mice. The congenic strains B10.M and B10.Q were found to be high responders, whereas B10.BR and B10.P were low responders. F1 (B10.M X C57BL/10J) and F1 (B10.Q X C57BL/10J) hybrid mice were found to be low responders, similar to the C57BL/10J parent, indicating that the low responsive trait is dominant. Whereas B10.BR mice were shown to be low responders to M. leprae, B10.AKM and B10.A(2R) were clearly high responders, indicating that the H-2D region influences the magnitude of the T cell proliferative response. Gene complementation within the H-2 region was evident. Genes outside the H-2 region were also shown to influence the response to M. leprae. C3H/HeN were shown to be high responder mice, whereas other H-2k strains, BALB.K, CBA/N, and B10.BR, were low responders. Gene loci that influence the T cell proliferation assay have been discussed and were compared to known background genes which may be important for the growth of intracellular parasites. Because mycobacteria are intracellular parasites for antigen-presenting cells, genes that affect bacterial growth in these cells will also influence subsequent immune responses of the host.

Animals↗
PubMed1982

Genetics of murine resistance to Trypanosoma cruzi.

Resistance to the protozoan parasite Trypanosoma cruzi is governed by multiple genetic factors, including at least one coded for by a locus in or near the major histocompatibility complex of the mouse. The influence of the H-2 locus on resistance was evident when H-2 congenic mice on a strain background of intermediate resistance were challenged or when the survival of H-2 typed F2 mice was followed. The H-2k haplotype of the susceptible C3H/An strain was associated with higher mortality when compared with the H-2b haplotype of the resistant C57BL/10 strain. Genetic studies showed that resistance was a dominant trait and increased with genetic heterozygosity. F1 mice derived from crosses between resistant and susceptible strains, or even between two susceptible strains, were much more resistant than either parent. Crosses between two resistant strains, C57BL/6J and DBA/2J, led to resistant progeny in the F1 and F2 generations; but when recombinant inbred strains derived from these parental strains were challenged, susceptible strains were identified, indicating that different genes were responsible for resistance in the two strains.

Animals↗
PubMed2001

The development of a Th1-type response and resistance to Leishmania major infection in the absence of CD40-CD40L costimulation.

CD40-CD40L interactions have been shown to be essential for the production of IL-12 and IFN-gamma and control of L. major infection. In contrast, C57BL/6 mice deficient in CD28 develop a dominant Th1-type response and heal infection. In this study, we investigate the effects of a deficiency in both CD40L and CD28 molecules on the immune response and the course of L. major infection. We compared infection in mice genetically lacking CD40L (CD40L(-/-)), CD28 (CD28(-/-)), or both (CD40L(-/-)CD28(-/-)), and in C57BL/6 mice, all on a resistant background. Although CD40L(-/-) mice failed to control infection, CD28(-/-) and CD40L(-/-)CD28(-/-) mice, as well as C57BL/6 mice, spontaneously resolved their infections. Healing mice had reduced numbers of lesion parasites compared with nonhealing CD40L(-/-) mice. At wk 9 of infection, we detected similar levels of IL-4, IFN-gamma, IL-12p40, and IL-12Rbeta2 mRNA in draining lymph nodes of healing C57BL/6, CD28(-/-), and CD40L(-/-)CD28(-/-) mice, whereas CD40L(-/-) mice had increased mRNA levels for IL-4 but reduced levels for IFN-gamma, IL-12p40, and IL-12Rbeta2. In a separate experiment, blocking of the CD40-CD40L pathway using Ab to CD40L led to an exacerbation of infection in C57BL/6 mice, but had little or no effect on infection in CD28(-/-) mice. Together, these results demonstrate that in the absence of CD28 costimulation, CD40-CD40L interaction is not required for the development of a protective Th1-type response. The expression of IL-12p40, IL-12Rbeta2, and IFN-gamma in CD40L(-/-)CD28(-/-) mice further suggests the presence of an additional stimulus capable of regulating IL-12 and its receptors in absence of CD40-CD40L interactions.

Animals↗
PubMed1975

Biochemical, immunological and genetic studies in leprosy. II. Profile of immunoglobulins, complement components and C-reactive protein in sera of leprosy patients and healthy controls.

Various classes of immunoglobulins (IgA, IgM, IgG, IgD and IgE), complement components (C3 and C4) and C-reactive protein (CRP) were estimated in sera from normal healthy controls and leprosy (lepromatous and tuberculoid) patients from Ethiopia. Higher levels of IgA, IgM, IgG and IgD were found in lepromatous leprosy compared with normal healthy people while in tuberculoid leprosy only IgM, IgG and IgD levels were increased. Borderline leprosy patients showed increase in IgG level only. Although an increase in IgE was noted in lepromatous leprosy, it was not significant; the variations in IgE levels could be due to different socioeconomic background and exposure to intestinal parasites. C3 component was significantly reduced in leprosy patients compared with healthy controls while no difference in C4 component was observed. The results point towards an involvement of the "alternate pathway". A positive test against C-reactive protein antiserum was given by about 20% of the normal healthy controls while more than 60% lepromatous and tuberculoid leprosy patients were CRP positive. The results are discussed in relation to the status of immunoglobulins and complement components in leprosy and possible factors (environmental and genetic) which might affect them.

C-Reactive Protein↗
PubMed1980

Haemonchus contortus resistance in straightbred and crossbred Barbados Blackbelly sheep.

Resistance to Haemonchus contortus infection was studied in two experiments conducted with 52 lambs of widely different genetic background. Breed groups compared were: Dorset (D), Barbados Blackbelly (B), Dorset x Blackbelly (D x B), Suffolk x Blackbelly (S x B), Suffolk x Dorset x Blackbelly (S x D x B,[1/4 B]) and nonBlackbelly (NB, D and S). In each experiment, lambs were raised on concrete from birth and were essentially parasite free until infective larvae were administered. In Exp. 1, D x B, S x D x B and D wether lambs approximately 3 months old were infected with a standard dose of invective larvae estimated to be 98% H. contortus. D x B lambs had a longer (P < .05) prepatency period and, at necropsy 17-day postinfection, had a higher (P < .05) percentage of female parasites classified as immature than did the other breed groups. These data showed that the development of H. contortus larvae was inhibited in D x B host animals. In Exp. 2, B, D x B, S x B and NB ewe and wether lambs approximately 4 months old were treated with three sensitizing doses of H. contortus larvae. These were followed by a challenge infection. On the basis of fecal egg counts (eggs per gram feces, EPG), there was no evidence that the challenge infection induced a self-cure reaction in any breed group. All lambs with B breeding had significantly higher Hb levels at the end of the experiment than did NB lambs. b and S x B lambs had higher (P < .05) Hb levels than the D x B lambs, and B lambs had the highest (P < .05) mean corpuscular hemoglobin concentrations. Five days after the challenge infection, B, D x B and S x B lambs also had significantly higher white blood cell levels than did NB lambs. Significant sex differences were also observed in Exp. 2. Ewe lambs had lower final EPG levels, higher preinfection and postinfection Hb levels and higher maximum postinfection cosinophil levels. Breed x sex interactions for these parameters were not significant.

Abomasum↗
PubMed2001

Determinants for resistance and susceptibility to microfilaraemia in Litomosoides sigmodontis filariasis.

Filarial infections of humans are chronic diseases. Despite an ongoing immune response, adult filariae continuously produce their offspring, the microfilariae (Mf), which are able to persist in sufficient numbers to ensure transmission. In this study, host- and parasite-derived factors, which contribute to persistence of Mf, were investigated using the filariasis model of Litomosoides sigmodontis in mice. Different strains of mice were found to differ widely in their capability to eliminate circulating Mf. Studies of congenic mouse strains showed that early and rapid clearance of Mf was mediated by activation pathways relevant to innate immunity, whereas late or delayed clearance of Mf was pre-determined by MHC-related factors. Genetic knock-out of genes for the MHC class-II molecules totally abrogated resistance. Most interestingly, the presence of only I adult female, but not male worms, renders all mice susceptible, irrespective of the genetic background, enabling Mf to circulate for extended periods of time. Such prolonged microfilaraemia was also observed in L. sigmodontis-infected animals challenged with heterologous Mf of Acanthocheilonema viteae. The use of cytokine gene knock-out mice showed that persistence of L. sigmodontis Mf was facilitated by IL-10, but not by IL-4 or IFN-gamma. In conclusion, irrespective of a resistant or susceptible host genetic background, survival of Mf of L. sigmodontis in mice is decisively regulated by the presence of adult female L. sigmodontis which will skew and exploit immune responses to facilitate the survival and persistence of their offspring in the infected host.

Animals↗
PubMed1999

Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors.

BACKGROUND: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine-glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of new therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. RESULTS: The TR-trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH***O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine natural products that are novel TR inhibitors. CONCLUSIONS: The structure of the TR-trypanothione enzyme-substrate complex provides details of a potentially valuable drug target. This information has helped to identify a new class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.

Amino Acid Sequence↗
PubMed1997

Expression and immunogenicity of an Echinococcus granulosus fatty acid-binding protein in live attenuated Salmonella vaccine strains.

Fatty acid-binding proteins (FABPs) are candidate molecules for vaccines against several parasitic platyhelminths. A FABP from the cestode Echinococcus granulosus (EgDf1) was expressed in Salmonella vaccine strains as a C-terminal fusion to fragment C of tetanus toxin (TetC) by using expression vector pTECH. The fusion protein was equally expressed in several attenuated vaccine strains derived from bacteria with different genetic backgrounds and different attenuating mutations. Single-dose immunization experiments with the aroA Salmonella typhimurium strain SL3261 carrying the pTECH-EgDf1 construct were conducted with mice, using both the intravenous and the oral routes. Surprisingly, the antibody response to EgDf1 and the antigen-specific cytokine production in spleen cells were stronger in mice immunized orally. Furthermore, immune mouse sera strongly reacted with fixed sections of the worm's larval stage. Analysis of the isotype distribution of the specific anti-EgDf1 antibodies showed similar production of immunoglobulin G1 (IgG1) and IgG2a together with specific IgA antibodies. In addition, stimulation of spleen cells from mice immunized with the different constructs with either Salmonella lysate, TetC, or EgDf1 showed that, together with Th1-related cytokines (gamma interferon and interleukin 2 [IL-2]), significant levels of a Th2 cytokine (IL-5) were produced specifically, indicating a Th2 component to the response to the Salmonella carrier and to the recombinant antigens. Salmonellae expressing the TetC-rEgDfl fusion are currently under evaluation as potential vaccines against E. granulosus.

Animals↗
PubMed1995

T cell and non-T cell compartments can independently determine resistance to Leishmania major.

In experimental murine cutaneous leishmaniasis caused by Leishmania major (Lm), the cellular determinants governing development of protective or exacerbative T cells are not well understood. We, therefore, attempted to determine the influence of T cell and non-T cell compartments on disease outcome. To this end, T cell chimeric mice were constructed using adult thymectomized lethally irradiated, bone marrow-reconstituted (ATXBM) animals of genetically resistant, C57BL/6, or susceptible, BALB/c, backgrounds. These hosts were engrafted with naive T cell populations from H-2-congenic susceptible, BALB.B6-H-2b, or resistant, C57BL/6.C-H-2d, animals, respectively. Chimeric mice were then infected with Lm, and disease outcome was monitored. BALB/c T cell chimeric mice, BALB/c ATXBM hosts given naive C57BL/6.C-H-2d T cells, resolved their infections as indicated by reductions in both lesion size and parasite numbers. Furthermore, the mice developed typical Th1 (interferon[IFN]-gamma hiinterleukin[IL]-4lo) cytokine patterns. In contrast, both sham chimeric, BALB/c ATXBM hosts given naive BALB/c T cells, and control irradiated euthymic mice succumbed to infection, producing Th2 profiles (IFN-gamma loIL-4hiIL-10hi). C57BL/6 T cell chimeras, C57BL/6 ATXBM hosts given naive BALB.B6-H-2b T cells, resolved their infections as did C57BL/6 sham chimeras and euthymic controls. Interestingly, whereas C57BL/6 control animals produced Th1 cytokines, chimeric animals progressed from Th0 (IFN-gamma hiIL-4hiIL-10hi) to Th2 (IFN-gamma loIL-4hiIL-10hi) cytokine profiles as cure ensued. Both reconstitution and chimeric status of all mice were confirmed by flow cytometry. In addition, T cell receptor V beta usage of Lm-specific blasts was determined. In all cases, V beta use was multiclonal, involving primarily V beta 2, 4, 6, 8.1, 8.2, 8.3, 10, and 14, with relative V beta frequencies differing between H-2b and H-2d animals. Most importantly, however, these differences did not segregate between cure and noncure outcomes. These findings indicate that: (a) genetic traits determining cure in Lm infection can direct disease outcome from both T cell and non-T cell compartments; (b) the presence of the curing genotype in only one compartment is sufficient to confer cure; (c) curing genotype T cells autonomously assume a Th1 cytokine profile-mediating cure; (d) noncuring genotype T cells can mediate cure in a curing environment, despite the onset of Th2 cytokine production; and lastly, (e) antigen specificity of responding T cells, as assessed by V beta T cell receptor diversity, is not a critical determinant of disease outcome.

Animals↗
PubMed1999

Molecular epidemiology and evolutionary genetics of Leischmania parasites.

In order to illustrate the relevance of the concepts and methods of evolutionary genetics in the understanding of the epidemiology of pathogenic agents, we develop in this paper the case of the Leishmania, a genus of parasitic protozoa. An extensive study of various natural populations of Leishmania in different countries (Old and New World) was carried out by using Multilocus Enzyme Electrophoresis (MLEE) and Random Amplified Polymorphic DNA fingerprinting (RAPD) as genetic markers. The data have been interpreted in evolutionary genetic terms. The main benefit of this approach has been to better define the concept of species in the genus Leishmnania, on rigorous phylogenetic bases. As a matter of fact, a sound taxonomical background is a prerequisite for any epidemiological approach. Since the biological concept of species is difficult or impossible to apply for most pathogenic microorganisms, we recommend relying on criteria of both phylogenetic discreteness and of epidemiological/medical relevance to describe new species of Leishmania. Through this approach, for example, we have shown that the species status of L. ( V.) perzzl.ianza can be supported. On the contrary, we have been unable to clearly distinguish L. (V.) panamensis from L. (V.) guyanensis with genetic tools. Additionally, we have shown that the epidemiological inferences based on a limited set of genetic markers can be misleading. As a matter of fact, we have demonstrated that a collection of L. (L.) infantum stocks identified as zymodeme 'MON 1' by other authors present additional genetic heterogeneity and do not correspond to a distinct 'Discrete Typing Unit' DTU, and are actually polyphyletic. Lastly, in the samples that were conveniently designed, we have confirmed that Leishmania parasites have a basically clonal population structure. As the clonal model specifies it, occasional bouts of genetic exchange remain nevertheless possible. Telling comparisons are drawn with the evolutionary genetics of other pathogens Trypanosoma cruzi and Trypanosoma congolense.

Animals↗
PubMed2000

Adoptive transfer of immunity with intraepithelial lymphocytes in Cryptosporidium parvum-infected severe combined immunodeficient mice.

BACKGROUND: Intestinal infections with the protozoan parasite Cryptosporidium parvum are prevalent in both immunocompetent and immunocompromised hosts. Although C parvum is an important cause of outbreaks and opportunistic infections worldwide, little is known about protective mucosal immune responses. This is in part because animal models of infection are limited to those with genetic or induced immunodeficiencies. METHOD: In this report, we isolated immune (primed) or nonimmune (unprimed) intraepithelial lymphocytes (IEL) from BALB/cJ mouse intestines, adoptively transferred them into C parvum-infected severe combined immunodeficient (SCID) mice, and evaluated infection and cell phenotype responses. RESULTS: Control SCID mice that received no IEL shed large numbers of oocysts throughout the experimental period (day 18 to day 72). Transfer of primed IEL significantly reduced fecal oocyst shedding in recipient SCID mice compared with SCID mice that received unprimed IEL or no IEL. SCID mice transferred with unprimed IEL shed variable numbers of fecal oocysts that increased and decreased in bursts until day 57 after infection. SCID mice transferred with primed IEL exhibited significantly higher proportions of T-cell receptor (TCR) alphabeta+, CD8+, and CD8alphabeta+ EL compared with inoculated SCID mice that received unprimed or no IEL. CONCLUSION: We conclude that primed IEL from immunocompetent mice may influence protective mucosal response against cryptosporidiosis when transferred into SCID mice. In addition, the increased percentage of TCR alphabeta+, CD8+, CD8alphabeta+ IEL in recipient SCID mice may reflect mucosal cell populations involved in these responses during chronic C parvum infection.

Adoptive Transfer↗
PubMedDate not supplied

[The role of atopic background in the genesis of allergic manifestations in intestinal parasitoses].

The previous literature and personal observations showed the predominant role of the atopic background in the appearance of the allergic manifestation in the parasitic infestation and especially in giardiasis. The lot investigated was made of 52 patients with allergic manifestations, also infested with Giardia intestinalis or with Ascaris lumbricoides. The hereditary collateral and personal allergic antecedents and the clearly deficient histaminopexy (1/20) were present in 1/2 of the patients. Summation of the various parameters of atopic background shows its presence in about 2/3 of the patients investigated. Association of the clinical involvement of trophallergens was present in 1/2 of the patients. The results show that the allergic manifestation in the intestinal parasitoses have a multifactorial determination. The atopic background is predominant in their development. These manifestations are often a result of alimentary allergy due to the absorption of alimentary antigens through the enteral mucous membrane affected by the parasite.

Ascariasis↗
PubMed2000

Interleukin-5 is essential for vaccine-mediated immunity but not innate resistance to a filarial parasite.

The study of protective immune mechanisms effective against filarial nematodes has been hampered by the inability of these important human pathogens to infect laboratory mice. Recently, Litomosoides sigmodontis, a natural parasite of rats, has been developed as a valuable model for the study of filarial infection. BALB/c mice are fully susceptible to infection with L. sigmodontis third-stage larvae and develop patent infection. In contrast, mice on the C57BL background are resistant, and parasites undergo only a single molt and do not mature to adulthood. We used interleukin-5 (IL-5)-deficient mice on the C57BL/6 background to address the role of IL-5 and eosinophils in the innate resistance of C57BL/6 mice. We found no differences in parasite survival between IL-5-deficient and C57BL/6 mice. However, when these mice were used for the analysis of vaccine-mediated immunity, a critical role for IL-5 was elucidated. Mice genetically deficient in IL-5 were unable to generate a protective immune response when vaccinated with irradiated larvae, whereas C57BL/6 mice were fully protected from challenge infection. These studies help to clarify the highly controversial role of eosinophils in filarial infection.

Animals↗
PubMed1997

Imbalanced distribution of Plasmodium falciparum MSP-1 genotypes related to sickle-cell trait.

BACKGROUND: The sickle-cell trait protects against severe Plasmodium falciparum malaria and reduces susceptibility to mild malaria but does not prevent infection. The exact mechanism of this protection remains unclear. We have hypothesized that AS individuals are protected by virtue of being less susceptible to a subset of parasite strains; thus we compared some genetic characteristics of parasites infecting AS and AA subjects. MATERIALS AND METHODS: Blood was collected from asymptomatic individuals living in two different regions of Africa. The polymorphic MSP-1 and MSP-2 loci were genotyped using a PCR-based methodology. Individual alleles were identified by size polymorphism, amplification using family-specific primers, and hybridization using family-specific probes. Multivariate logistic regression was used to analyze allele distribution. RESULTS: In Senegalese carriers, age and hemoglobin type influenced differently the distribution of the three MSP-1 families and had an impact on distinct individual alleles, whereas the distribution of MSP-2 alleles was marginally affected. There was no influence of other genetic traits, including the HLA Bw53 genotype, or factors such as place of residence within the village. In a cohort of Gabonese schoolchildren in which the influence of age was abrogated, a similar imbalance in the MSP-1 allelic distribution but not of MSP-2 allelic distribution by hemoglobin type was observed. CONCLUSIONS: The influence of the host's hemoglobin type on P. falciparum genotypes suggests that parasite fitness for a specific host is strain-dependent, which is consistent with our hypothesis that innate resistance might result from reduced fitness of some parasite strains for individuals with sickle-cell traits.

Adolescent↗