Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. II. Immunobiological Dysfunctions

Blom-Potar, Marie Christine; Chamond, Nathalie; Cosson, Alain; Jouvion, Grégory; Droin-Bergère, Sabrina; Huerre, Michel; Minóprio, Paola

doi:10.1371/journal.pntd.0000793

Cited by 29 publications

(34 citation statements)

References 46 publications

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“…However, the light emissions we measured clearly demonstrated that growing parasites were accumulating close to the inoculation site. The results we obtained with bioluminescent T. vivax are fully consistent with our previous reports [10] and confirm that the parasite spreads across the spleen and liver compartments. It is interesting to note that lung infiltration by the parasite is difficult or impossible to observe by immunohistopathology, contrasting with our present observations.…”

Section: Discussionsupporting

confidence: 92%

“…We have previously developed experimental models of T. vivax infection using mice infected with the ILRAD1392 reference strain [9]. Immunobiological and immunophysiopathological analyses confirmed that these models are reliable and consistent with all the relevant characteristics of the animal disease [9], [10]. Furthermore, we have also developed robust methods for parasite growth and differentiation in axenic cultures, paving the way to appropriate conditions for the first genetic manipulation of T. vivax [11].…”

Section: Discussionmentioning

confidence: 85%

“…In efforts to overcome the problems encountered when studying T. vivax infection and pathology in the field, we recently developed murine models that deliver sustained and reproducible infections which successfully mimic the parasitological, histological and pathological features of the infection and closely resemble those observed in cattle trypanosomosis [9], [10]. For instance, histopathological examinations performed throughout the infective process showed many necrotic foci in lymphoid and non-lymphoid organs with extravasated blood cells and trypanosomes in hemorrhagic spots.…”

Section: Introductionmentioning

confidence: 99%

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Non-Invasive In Vivo Study of the Trypanosoma vivax Infectious Process Consolidates the Brain Commitment in Late Infections

et al. 2013

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Trypanosoma vivax, one of the leading parasites responsible for Animal African Trypanosomosis (Nagana), is generally cyclically transmitted by Glossina spp. but in areas devoid of the tsetse flies in Africa or in Latin American countries is mechanically transmitted across vertebrate hosts by other haematophagous insects, including tabanids. We followed on from our recent studies on the maintenance of this parasite in vivo and in vitro, and its genetic manipulation, by constructing a West African IL1392 T. vivax strain that stably expresses firefly luciferase and is fully virulent for immunocompetent mice. We report here on a study where murine infection with this strain was monitored in vivo using a non-invasive method. Study findings fully support the use of this strain in the assessment of parasite dynamics in vivo since a strong correlation was found between whole body light emission measured over the course of the infection and parasitemia determined microscopically. In addition, parasitemia and survival rates were very similar for mice infected by the intraperitoneal and sub-cutaneous routes, except for a longer prepatent period following sub-cutaneous inoculation with the parasite. Our results clearly show that when administered by the subcutaneous route, the parasite is retained few days in the skin close to the inoculation site where it multiplies before passing into the bloodstream. Ex vivo bioluminescence analyses of organs isolated from infected mice corroborated our previous histopathological observations with parasite infiltration into spleen, liver and lungs. Finally, our study reinforces previous observations on the presence of the parasite in the central nervous system and consequently the brain commitment in the very late phases of the experimental infection.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Non-Invasive In Vivo Study of the Trypanosoma vivax Infectious Process Consolidates the Brain Commitment in Late Infections

et al. 2013

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“…We used this IL 1392 strain to establish novel mouse models of experimental infection and immunopathology [7], [8]. Today, we report herein on how we managed to overcome the lack of genetic tools for analyzing T. vivax gene expression and function by standardizing the axenic conditions for epimastigote cultivation of the IL 1392 strain and its in vitro differentiation into infectious forms.…”

Section: Discussionmentioning

confidence: 99%

Genetic Engineering of Trypanosoma (Dutonella) vivax and In Vitro Differentiation under Axenic Conditions

D’Archivio¹,

Medina²,

Cosson³

et al. 2011

PLoS Negl Trop Dis

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Trypanosoma vivax is one of the most common parasites responsible for animal trypanosomosis, and although this disease is widespread in Africa and Latin America, very few studies have been conducted on the parasite's biology. This is in part due to the fact that no reproducible experimental methods had been developed to maintain the different evolutive forms of this trypanosome under laboratory conditions. Appropriate protocols were developed in the 1990s for the axenic maintenance of three major animal Trypanosoma species: T. b. brucei, T. congolense and T. vivax. These pioneer studies rapidly led to the successful genetic manipulation of T. b. brucei and T. congolense. Advances were made in the understanding of these parasites' biology and virulence, and new drug targets were identified. By contrast, challenging in vitro conditions have been developed for T. vivax in the past, and this per se has contributed to defer both its genetic manipulation and subsequent gene function studies. Here we report on the optimization of non-infective T. vivax epimastigote axenic cultures and on the process of parasite in vitro differentiation into metacyclic infective forms. We have also constructed the first T. vivax specific expression vector that drives constitutive expression of the luciferase reporter gene. This vector was then used to establish and optimize epimastigote transfection. We then developed highly reproducible conditions that can be used to obtain and select stably transfected mutants that continue metacyclogenesis and are infectious in immunocompetent rodents.

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“…However, recent studies have suggested that such genetically identical mice may not serve as an accurate model for the human condition (which are generally outbred) in terms of their immune responses. [10][11][12] To evaluate the utility of the inbred mouse model, outbred mice were also analyzed in these experiments. Both inbred and outbred mice were lethally irradiated and syngeneic BMT (the optimal situation) was performed.…”

Section: Introductionmentioning

confidence: 99%

The Immune Response in Inbred and Outbred Strains of Mice before and after Bone Marrow Transplantation

Shultz¹,

Badowski²,

Harris³

2013

CTTT

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Abstract:Understanding the immune response is critical to evaluate the response to infection and vaccines, particularly in bone marrow transplant (BMT) recipients who may exhibit an altered immune system. Such studies have relied upon inbred mouse models due to genetic consistency and experimental reproducibility. Recent studies suggest that inbred mice vary substantially from outbred counterparts in terms of immune responses. These experiments quantified differences in immune responses of inbred and outbred mice before and after BMT. Inbred and outbred adult mice were lethally irradiated and syngeneic bone marrow transplants performed. 6-9weeksafterengraftment,themicewereimmunizedwithallogeneiccells.Immunecellchangeswereanalyzedbyflowcytometry. Immunizationresultedinsignificantleukocyteincreasesinallgroups.Bcellsonlyvariedfortransplantedinbredmice.Outbredmice hadsignificantlygreaterbaselineTcellsduetoincreasedCD4+Tcells.CD8+ T cell numbers were comparable between the strains and groups.Interestingly,inoutbredmicebothCD4andCD8TcellsrespondedequallywhileininbredmiceCD8Tcellswere predominant. Outbredmicehadpeakresponseslaterandmoreprolongedthaninbredmice.Thus,inbredmicemaynotbeanaccuratemodelfor testing immune responses in humans, especially after BMT.

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Trypanosoma vivax Infections: Pushing Ahead with Mouse Models for the Study of Nagana. II. Immunobiological Dysfunctions

Cited by 29 publications

References 46 publications

Non-Invasive In Vivo Study of the Trypanosoma vivax Infectious Process Consolidates the Brain Commitment in Late Infections

Non-Invasive In Vivo Study of the Trypanosoma vivax Infectious Process Consolidates the Brain Commitment in Late Infections

Genetic Engineering of Trypanosoma (Dutonella) vivax and In Vitro Differentiation under Axenic Conditions

The Immune Response in Inbred and Outbred Strains of Mice before and after Bone Marrow Transplantation

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