Canine visceral leishmaniasis: successful chemotherapy induces macrophage antileishmanial activity via the L-arginine nitric oxide pathway

Vouldoukis, Ioannis; Drapier, Jean‐Claude; Nüssler, Andreas K.; Tselentis, Yiannis; Silva, O A Da; Gentilini, M; Mossalayi, Djavad; Monjour, L; Dugas, Bernard

doi:10.1128/aac.40.1.253

Cited by 52 publications

(33 citation statements)

References 22 publications

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“…Therefore, a glutathione redox imbalance has been associated with immune system dysregulation, which may then indicate that it not only plays a role in promoting the pathophysiology of the disease, but also that once animals enter this uncontrolled state it is progressively more difficult for their immune systems to control the parasite [67-69]. This may partly explain the fact that after successful chemotherapy of canine leishmaniasis the ability to mount an effective Th1-dominated immune response is once again restored [29]. For this reason, oxidative stress represents an interesting surrogate marker of the level of dysregulation in the immune system during the control of the infection as well as an indicator of damage being done to vital tissues.…”

Section: Discussionmentioning

confidence: 99%

The protective immune response produced in dogs after primary vaccination with the LiESP/QA-21 vaccine (CaniLeish®) remains effective against an experimental challenge one year later

Martin

Vouldoukis

Moreno

et al. 2014

Vet Res

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Control of canine leishmaniasis is an important objective for the benefit of dogs living in or visiting endemic areas and for public health because of the zoonotic nature of this disease. Resistance or susceptibility to developing canine leishmaniasis after exposure to Leishmania infantum is primarily determined by the ability of the immune system to develop an appropriate Th1-dominated specific response to the parasite. For this reason there is a need for effective canine vaccines that can decrease the number of dogs developing progressive infections. In this study, we followed the impact of the LiESP/QA-21 canine vaccine (composed of excreted-secreted proteins of L. infantum and the QA-21 saponin adjuvant), recently launched commercially in Europe, on selected humoral and cellular immune parameters following an infectious intravenous challenge with L. infantum promastigotes administered one year after the primary vaccine course. We also followed parasitological parameters to determine the parasitological status of the challenged dogs. In contrast to controls, vaccinated dogs retained significantly stronger cell-mediated immune responses against the parasite despite a virulent challenge and had significantly lower mean parasite burdens at the end of the study, associated with a lower probability of developing active infections. These results confirm that the immune responses generated by vaccination with LiESP/QA-21 are still effective against an intravenous challenge one year after the primary vaccine course.

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Section: Discussionmentioning

confidence: 99%

The protective immune response produced in dogs after primary vaccination with the LiESP/QA-21 vaccine (CaniLeish®) remains effective against an experimental challenge one year later

Martin

Vouldoukis

Moreno

et al. 2014

Vet Res

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show abstract

“…This has been demonstrated following successful chemotherapy of L. infantum dogs (Vouldoukis et al 1996). Anti-leishmanial activity and NO production were also detected in a canine macrophagic cell line infected with L. infantum after incubation with IL-2, IFN- γ and TNF- α (Pinelli et al 2000).…”

Section: Innate Immune Responsesmentioning

confidence: 92%

Insights on adaptive and innate immunity in canine leishmaniosis

2016

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SUMMARYCanine leishmaniosis (CanL) is caused by the parasite Leishmania infantum and is a systemic disease, which can present with variable clinical signs, and clinicopathological abnormalities. Clinical manifestations can range from subclinical infection to very severe systemic disease. Leishmaniosis is categorized as a neglected tropical disease and the complex immune responses associated with Leishmania species makes therapeutic treatments and vaccine development challenging for both dogs and humans. In this review, we summarize innate and adaptive immune responses associated with L. infantum infection in dogs, and we discuss the problems associated with the disease as well as potential solutions and the future direction of required research to help control the parasite.

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“…The main effector mechanism involved in the protective immune response of dogs infected with L. infantum is the activation of macrophages by IFN-γ and TNF-α to kill intracellular amastigotes via the L-arginine nitric oxide pathway, as has been observed following successful chemotherapy of L. infantum -infected dogs 112 . NO production and anti-leishmanial activity has also been detected in a canine macrophage cell line infected with L. infantum after incubation with IFN-γ, TNF-α and IL-2 88 , as well as in macrophages from dogs immunized with killed L.infantum promastigotes 82 .…”

Section: Dog Modelmentioning

confidence: 99%

Animal Models for the Study of Leishmaniasis Immunology

Loría-Cervera

Andrade-Narvaez

2014

Rev. Inst. Med. trop. S. Paulo

135

101

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Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

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Canine visceral leishmaniasis: successful chemotherapy induces macrophage antileishmanial activity via the L-arginine nitric oxide pathway

Cited by 52 publications

References 22 publications

The protective immune response produced in dogs after primary vaccination with the LiESP/QA-21 vaccine (CaniLeish®) remains effective against an experimental challenge one year later

The protective immune response produced in dogs after primary vaccination with the LiESP/QA-21 vaccine (CaniLeish®) remains effective against an experimental challenge one year later

Insights on adaptive and innate immunity in canine leishmaniosis

Animal Models for the Study of Leishmaniasis Immunology

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