Mechanisms of development of immunosuppression during Trypanosoma infections

Sztein, Marcelo B.; Kierszenbaum, Felipe

doi:10.1016/0169-4758(93)90053-i

Cited by 28 publications

(16 citation statements)

References 37 publications

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“…Sin embargo, el mayor impacto se observa en parásitos que por su naturaleza intracelular, o su acción directa interna sobre órganos vitales, son profundamente afectados por cualquier alteración en la inmunidad celular, blanco fundamental de la inmunosupresión (Ferreira & Borges 2002, Dedet & Pratlong 2005. Tal es el caso de los tripanosomas del grupo Salivaria (africanos) (Uzonna et al 1998), (Trypanosoma cruzi (Krettli 1977, Sztein & Kierszenbaum 1993, Bacal et al 2010, Leishmania spp. (Oliveira et al 2008), Toxoplasma gondii (Abedalthagafi et al 2009, García et al 2010, Soléne et al 2010 y Plasmodium falciparum (Grimwade et al 2004).…”

Section: Resultsunclassified

Efecto inmunosupresor de la infección por <i>Trypanosoma musculi</i> (Mastigophora: Trypanosomatidae) en la toxoplasmosis experimental

Piccolo-Johanning

Kellerman-Guterman

Valerio-Campos

et al. 2013

RBT

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Immunosuppressor effect of Trypanosoma musculi (Mastigophora: Trypanosomatidae) on experimental toxoplasmosis. The immunosuppression caused by species of the gender Trypanosoma has been widely documented. The influence over experimental infections with Toxoplasma gondii is evident when using Trypanosoma lewisi, a natural parasite of white rats. We decided to test the effect of Trypanosoma musculi from mice, an organism with very similar biological characteristics to T. lewisi, to see if this trypanosomatid could induce a similar effect. Four groups of Swiss mice were inoculated with T. musculi previously to infection with T. gondii, and we determined the survival of the animals, as well as the number of cysts developed in the brain of survivors. We isolated and tested different strains of T. gondii from different sources. In a first experiment, the animals were previously inoculated with T. musculi at different times prior to the infection with Toxoplasma; this allowed us to determine that the immunosuppression process resulted more evident when T. musculi inoculation was made four days before. In a second experiment, we used different inoculi dose and found that it did not influenced the process. Furthermore, the results were negative when evaluating if the amount of the inoculated trypomastigote influenced the process. In order to demonstrate if there were differences in the immnosuppressive effect, related to Toxoplasma strains, groups of mice were inoculated with brain cysts of TFC, TLP, TLW and TBT strains. Excluding the TLP strain, that resulted to be very pathogenic regardless the previous inoculation with T. lewisi, the other strains kept the same pattern of immunosuppression in mice, whose survival time was shorter as the presence of cysts in the brain was higher. These observations were in agreement with an experimental immunosuppression model, associated with immunosuppressive diseases, specially cancer and AIDS. Rev. Biol. Trop. 61 (2): 981-990. Epub 2013 June 01.

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Section: Resultsunclassified

Efecto inmunosupresor de la infección por <i>Trypanosoma musculi</i> (Mastigophora: Trypanosomatidae) en la toxoplasmosis experimental

Piccolo-Johanning

Kellerman-Guterman

Valerio-Campos

et al. 2013

RBT

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“…We find that our basic qualitative result (that there is a diversity threshold for cross-immunity, which divides the outcomes into a regime in which variant-specific immunity is dominant from one in which cross-reactive immunity is dominant) is maintained even when we modify the proliferation term for immune cells in a variety of ways-including (i) changing the term to pp as in the case of published models of HIV dynamics (18); (ii) removing the saturation in the term for the generation of immune responses (i.e., changing the term to the form ppixi); (iii) adding to the proliferation term a constant (small) input of naive immune cells from the thymus (in this case neither cross-nor specific-immunity tend to zero before and after diversity threshold is breached, but rather they fall to low levels); and (iv) introducing competition between the various immune responses by having a carrying capacity that limits the total immune response-then we can observe suppression of all immune responses when the parasite density is high. This last modification could provide a simple explanation for the generalized immunosuppression reported in the literature (29,30) and may also give rise to an increase in the duration of infection.…”

Section: Discussionmentioning

confidence: 99%

Antigenic variation and the within-host dynamics of parasites.

Antia

Nowak²,

Anderson³

1996

Proc. Natl. Acad. Sci. U.S.A.

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Many parasites exhibit antigenic variation within their hosts. We use mathematical models to investigate the dynamical interaction between an antigenically varying parasite and the host's immune system. The models incorporate antigenic variation in the parasite population and the generation of immune responses directed against (i) antigens specific to individual parasite variants and (ii) antigens common to all the parasite variants. Analysis of the models allows us to evaluate the relative importance of variantspecific and cross-reactive immune responses in controlling the parasite. Early in the course of infection within the host, when parasite diversity is below a defined threshold value (the value is determined by the biological properties of the parasite and of the host's immune response), the variant-specific immune responses are predominant. Later, when the parasite diversity is high, the cross-reactive immune response is largely responsible for controlling the parasitemia. It is argued that increasing antigenic diversity leads to a switch from variantspecific to cross-reactive immune responses. These simple models mimic various features of observed infections recorded in the experimental literature, including an initial peak in parasitemia, a long and variable duration of infection with fluctuating parasitemia that ends with either the clearance of the parasite or persistent infection.As molecular techniques are used more widely in epidemiological studies of infectious diseases, antigenic variability is found in many host-parasite associations (1-3). The production of immunologically novel parasite strains or variants can affect the dynamics of parasite populations at both the between-host and the within-host levels. At the between-host or epidemiological level, the generation of antigenically different strains (which elicit little or limited cross-immunity in the host) will allow the infection of individual hosts with several distinct parasite strains, thus increasing the possible size of the parasite population within the host community (4, 5). The influenza viruses (6), the cholera bacillus Vibro cholerae (7), the malaria parasite Plasmodium falciparum (8), and Giardia lamblia, the protozoan that causes Giardiasis (9), exhibit strain variation in human populations. At the within-host level, the rapid generation of antigenic variants can enhance the likelihood of parasite persistence in the face of a hostile immune response, thereby prolonging the duration of infectiousness and concomitantly increasing the potential for transmission to a new host. The protozoans Trypanosoma brucei (10,11) (21,22). As can be seen in Fig. 1 the dynamics of T. vivax within its natural host (cattle) begins with a rapid rise in parasitemia, which is followed by a long and variable duration of infection and the eventual clearance of the parasite or its control at very low densities. In addition to the complex pattern of parasitemia, we observe a large diversity in the profiles of parasitemia in different individuals...

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“…The difference in immune responses including the function of FasL-producing cells during the course of malaria infection might explain the difference in susceptibility between Japanese macaques and cynomolgus macaques. As described for other infectious diseases (13,19,23,27), falciparum malaria infection also induces host immune dysfunction including a decreased number of circulating T cells (3,7,9,26) and in vitro depression of proliferative response of PBMCs to parasite antigens (17,22), which may be responsible for the severe disease of the patients with falciparum malaria. In fact, T lymphocytopenia is also considered one of the typical features of human acute falciparum malaria, and the degree of T lymphocytopenia is correlated with disease severity: it is higher in patients with severe malaria and those with cerebral malaria than in patients with uncomplicated malaria (9).…”

Section: Vol 68 2000mentioning

confidence: 99%

Malaria Infection Induces Rapid Elevation of the Soluble Fas Ligand Level in Serum and Subsequent T Lymphocytopenia: Possible Factors Responsible for the Differences in Susceptibility of Two Species ofMacacaMonkeys toPlasmodium coatneyiInfection

Matsumoto

Kawai

Terao³

et al. 2000

Infect Immun

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The intraerythrocytic stage of the simian malaria parasite Plasmodium coatneyi (CDC strain) was intravenously inoculated into two species of macaques with different susceptibilities to infection with this parasite, including four Japanese macaques (Macaca fuscata) and three cynomolgus macaques (M. fascicularis). The Japanese macaques infected with P. coatneyi developed severe clinical manifestations similar to those of severe human malaria and eventually became moribund, while the infected cynomolgus macaques, natural hosts of the parasite, exhibited no severe manifestation of disease except anemia and finally recovered from the infection. In the infected Japanese macaques, peripheral CD4؉ and CD8 ؉ T-cell populations were markedly decreased and fragmentation of chromosomal DNA in peripheral blood mononuclear cells was detected during the terminal period of infection, suggesting that apoptotic cell death was responsible at least in part for the T lymphocytopenia. Furthermore, soluble Fas ligand levels in sera of the infected Japanese macaques increased gradually to a markedly high level of 28.83 ؎ 10.56 pg/ml (n ‫؍‬ 4) when the animals became moribund. On the other hand, none of the infected cynomolgus monkeys exhibited either T lymphocytopenia or elevated soluble Fas ligand level. These findings suggest that differences in immune response between the two species of macaque tested accounted for the contrasting outcomes after infection with the same isolate of malarial parasite, and in particular that a profound T lymphocytopenia due to Fas-derived apoptosis played a role in the fatal course of malaria in the infected Japanese macaques.Plasmodium falciparum infection leads to severe signs and symptoms and a wide variety of clinical consequences, but not every patient becomes seriously ill or dies (28). The outcome of infection is influenced by individual susceptibility, parasite virulence, and a number of environmental factors, and recent intensive studies on the factors responsible for resistance to malarial infection have elucidated some effects of host genetic background on outcome of infection as well (8,16).P. coatneyi, a simian malarial parasite, causes mild infection in its natural host, the cynomolgus macaque (Macaca fascicularis) (4), but more serious infection in experimental hosts such as the Japanese macaque (M. fuscata) (11) and rhesus macaque (M. mulatta) (1). In the latter two species, infected monkeys develop a fulminating acute infection with pronounced parasitemia and became moribund with severe manifestations. Furthermore, they exhibit histopathological findings typical of cerebral malaria: sequestration of parasitized red blood cells and cytoadherence-associated knobs on parasitized red cells to endothelial cells were found in cerebral microvessels and capillaries of major organs in these monkeys. Japanese macaques and rhesus macaques infected with P. coatneyi can thus be used as powerful primate models for the pathophysiological study of severe human malaria.The Japanese macaque belongs to th...

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Mechanisms of development of immunosuppression during Trypanosoma infections

Cited by 28 publications

References 37 publications

Efecto inmunosupresor de la infección por <i>Trypanosoma musculi</i> (Mastigophora: Trypanosomatidae) en la toxoplasmosis experimental

Efecto inmunosupresor de la infección por <i>Trypanosoma musculi</i> (Mastigophora: Trypanosomatidae) en la toxoplasmosis experimental

Antigenic variation and the within-host dynamics of parasites.

Malaria Infection Induces Rapid Elevation of the Soluble Fas Ligand Level in Serum and Subsequent T Lymphocytopenia: Possible Factors Responsible for the Differences in Susceptibility of Two Species ofMacacaMonkeys toPlasmodium coatneyiInfection

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