Resistance to Plasmodium chabaudi in B10 mice: influence of the H-2 complex and testosterone

Wunderlich, Frank; Mossmann, Horst; Helwig, Michael; Schillinger, G

doi:10.1128/iai.56.9.2400-2406.1988

Cited by 85 publications

(32 citation statements)

References 38 publications

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“…Te even increases the susceptibility towards arthropod ectoparasites such as ticks (Ali & Sweatman 1966). Recently, a crucial role of Te has also been documented in the outcome of murine malaria caused by Plasmodium chabaudi (Wunderlich et al 1988) and P . berghei (Kamis & Ibrahim 1989).…”

Section: Introductionmentioning

confidence: 99%

“…There are numerous findings showing that Te exerts suppressive activities on diverse humoral and cellular immune reactions both in oiuo and in uifro (Kotani, Nawa & Fujii 1974, Morton et al 1981, Weinstein & Berkovich 1981, Dunkel et al 1985, Rife et al 1990). Thus, it has been suggested that Te prevents self-healing of P. chabaudi infections by suppressing the development of protective immunity (Wunderlich et al 1988). Alternatively, however, it is also possible that protective immune mechanisms are mounted even under Tetreatment, but these do not take effect for unknown reasons.…”

Section: Introductionmentioning

confidence: 99%

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Testosterone‐unresponsiveness of existing immunity against Plasmodium chabaudi malaria

Wunderlich

Benten

Bettenhaeuser

et al. 1992

Parasite Immunology

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Testosterone (Te) is known to suppress immunity and to increase host susceptibility to many parasites. This study investigates the action of Te on immunity acquired against blood-stages of the malaria parasite Plasmodium chabaudi in female mice of the inbred strain C57BL/10. Our data show: (i) About 90% of mice infected with 10(6) P. chabaudi-infected erythrocytes are able to develop protective immune mechanisms which become evident in self-healing the infection. The capability of self-healing is lost when mice are pretreated with Te for 3 weeks. (ii) Mice which have self-healed infections acquire immunity to homologous rechallenge. Concomitantly, mice become Te-unresponsive in that their acquired immunity is not suppressible by Te-treatment. (iii) Flow cytometry reveals that Te-pretreatment entails an increase of CD8+ cells and a decrease of Ig+ cells by about 4% in spleens of non-immune mice. In immune mice, however, there is a Te-unresponsiveness of the percental distribution of splenic cell populations. (iv) Adoptive transfer experiments indicate that immunity is conferred by spleen cells, presumably non-T-cells. These cells are Te-unresponsive, since they exert their effect in Te-pretreated mice in the presence of Te. (v) Te-unresponsive immunity can be also transferred by serum, especially the IgG-fraction, obtained from immune mice. Our data demonstrate that Te prevents the development of protective immunity against P. chabaudi infections. However, when once established, protective immunity becomes unresponsive to Te. Our data suggest that the effector mechanisms of protective immunity involve Te-unresponsive B cells secreting protective IgG-antibodies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Testosterone‐unresponsiveness of existing immunity against Plasmodium chabaudi malaria

Wunderlich

Benten

Bettenhaeuser

et al. 1992

Parasite Immunology

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“…TESTOSTERONE HAS A suppressive effect on immune responses of vertebrates (for reviews, see refs [1][2][3][4] and increases susceptibility toward numerous infectious diseases (for reviews, see refs 5, 6). In the experimental malaria Plasmodium chabaudi, for example, the suppressive effect of testosterone manifests itself as a host conversion from resistance to susceptibility: normally self-healing infections result in a fatal outcome (7,8). Concomitantly, testosterone induces a change in T cells from a resistance-promoting phenotype to a susceptibility-mediating phenotype, thus enabling the T cells to mediate the suppressive effect of testosterone (9).…”

mentioning

confidence: 99%

Functional testosterone receptors in plasma membranes of T cells

Lieberherr²,

et al. 1999

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T cells are considered to be unresponsive to testosterone due to the absence of androgen receptors (AR). Here, we demonstrate the testosterone responsiveness of murine splenic T cells in vitro as well as the presence of unconventional cell surface receptors for testosterone and classical intracellular AR. Binding sites for testosterone on the surface of both CD4(+) and CD8(+) subsets of T cells are directly revealed with the impeded ligand testosterone-BSA-FITC by confocal laser scanning microscopy (CLSM) and flow cytometry, respectively. Binding of the plasma membrane impermeable testosterone-BSA conjugate induces a rapid rise (<5 s) in [Ca2+]i of Fura-2-loaded T cells. This rise reflects influx of extracellular Ca2+ through non-voltage-gated and Ni2+-blockable Ca2+ channels of the plasma membrane. The testosterone-BSA-induced Ca2+ import is not affected by cyproterone, a blocker of the AR. In addition, AR are not detectable on the surface of intact T cells when using anti-AR antibodies directed against the amino and carboxy terminus of the AR, although T cells contain AR, as revealed by reverse transcription-polymerase chain reactions and Western blotting. AR can be visualized with the anti-AR antibodies in the cytoplasm of permeabilized T cells by using CLSM, though AR are not detectable in cytosol fractions when using the charcoal binding assay with 3H-R1881 as ligand. Cytoplasmic AR do not translocate to the nucleus of T cells in the presence of testosterone, in contrast to cytoplasmic AR in human cancer LNCaP cells. These findings suggest that the classical AR present in splenic T cells are not active in the genomic pathway. By contrast, the cell surface receptors for testosterone are in a functionally active state, enabling T cells a nongenomic response to testosterone.

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“…The non-clonal line of P. chabaudi [40], resembles P. chabaudi AS in terms of restriction fragment length polymorphism as well as dihydrofolate reductase and cysteine protease sequence identities [41]. Moreover, the used line of P. chabaudi is self-healing as the AS clone, which is under control of genes of the H-2 complex and the non-H-2 background as well as sex and sex hormones of the infected mouse strain [42]. The Balb/c mice were infected with 10 6 P. chabaudiinfected erythrocytes.…”

Section: Protective Vaccinationmentioning

confidence: 99%

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

Delić

Wunderlich

Al‐Quraishy

et al. 2020

Preprint

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Background Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi . Blood-stage malaria induces extramedullary erythropoiesis in the liver. This study investigates how vaccination affects the course of malaria-induced expression of erythrocytic genes in the liver. Methods Female Balb/c mice were vaccinated at week 3 and week 1 before challenging with 10 6 P. chabaudi- parasitized erythrocytes. The non-infectious vaccine consisted of erythrocyte ghosts isolated from P. chabaudi -infected erythrocytes. Gene expression microarrays and quantitative real-time PCR were used to compare mRNA expression of different erythrocytic genes in the liver of vaccination-protected and non-protected mice during infections on days 0, 1, 4, 8, and 11 p.i. . Results Global transcriptomics analyses reveal vaccination-induced modifications of malaria-induced increases in hepatic gene expression on days 4 and 11 p.i.. On these days, vaccination also alters hepatic expression of the erythropoiesis-involved genes Ermap, Kel, Rhd , Rhag , Slc4a1, Gypa, Add2, Ank1, Epb4.1, Epb4.2, Epb4.9, Spta1, Sptb, Tmod1 , Ahsp, Acyp1 , Gata1, Gfi1b, Tal1, Klf1, Epor , and Cldn13 . In vaccination-protected mice, expression of these genes, except Epb4.1 , is significantly higher on day 4 p.i. than in un-protected non-vaccinated mice, reaches maximal expression at peak parasitaemia on day 8 p.i., and is slowed down or even decreased towards the end of crisis phase on day 11 p.i.. After day 1 p.i., Epor expression takes about the same course as that of the other erythroid genes. Hepatic expression of Epo, however, is delayed in both vaccinated and non-vaccinated mice for the first 4 days p.i. and is maximal at significantly higher levels in vaccinated mice on day 8 p.i. , before declining towards the end of crisis phase on day 11 p.i. . Conclusion The present data indicate that vaccination accelerates malaria-induced erythroblastosis in the liver for 1-2 days. This may contribute to earlier replenishment of peripheral red blood cells by liver-derived reticulocytes, which may favour final survival of otherwise lethal blood-stage malaria, since reticulocytes are not preferred as host cells by P. chabaudi .

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Resistance to Plasmodium chabaudi in B10 mice: influence of the H-2 complex and testosterone

Cited by 85 publications

References 38 publications

Testosterone‐unresponsiveness of existing immunity against Plasmodium chabaudi malaria

Testosterone‐unresponsiveness of existing immunity against Plasmodium chabaudi malaria

Functional testosterone receptors in plasma membranes of T cells

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

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