The Predictive Validity of Naturally Acquired Delayed‐Type Hypersensitivity to Leishmanin in Resistance to<i>Leishmania major–</i>Associated Cutaneous Leishmaniasis

Salah, Afif Ben; Louzir, Hechmi; Chlif, Sadok; Mokni, M.; Zaâtour, Amor; Raouène, Mohamed; Ismail, R. Ben; Dellagi, Koussay

doi:10.1086/498042

Cited by 36 publications

(43 citation statements)

References 30 publications

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“…Interestingly, and quite unexpectedly, preimmunized groups in PWK and C57BL/6 mice did not develop positive DTH reaction to LTA despite cure in contrast to nonimmunized control groups. Discordance between cutaneous DTH (called the LST leishmanin skin test in humans) and disease or vice versa, is a well-known situation in natural (6,29,34) or experimental (8,20,30) disease.…”

Section: Vol 16 2009 Evaluation Of L Major Vaccine Candidates 1535mentioning

confidence: 99%

Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due toLeishmania majorInfection in Four Inbred Mouse Strains

Benhnini

Chenik

Laouini

et al. 2009

Clin Vaccine Immunol

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Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders that also support the development of experimental leishmaniasis due to L. major. In this study, we sought to determine whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins, namely, LACK (for Leishmania homolog of receptor for activated C kinase) and LmPDI (for L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c, and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in outbred human populations and should be selected for clinical trials.

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Section: Vol 16 2009 Evaluation Of L Major Vaccine Candidates 1535mentioning

confidence: 99%

Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due toLeishmania majorInfection in Four Inbred Mouse Strains

Benhnini

Chenik

Laouini

et al. 2009

Clin Vaccine Immunol

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“…Epidemics of CL in Tunisia may be associated with migration and the introduction of nonimmune people into lands with existing transmission [30]. Prediction of such outbreaks depends on the availability of ecological information and one valuation of development areas before implementation of projects or population movements.…”

Section: Transmission Of CLmentioning

confidence: 99%

“…It has been shown by several Tunisian epidemiological studies that the majority of human infections by Leishmania parasites remain asymptomatic, especially in endemic areas, indicating a high level of immunity of the residents in these regions [30]. Asymptomatic L. major infection constitutes a relatively frequent mode of natural immunization, and the ratio of asymptomatic infection to patent ZCL may reach approximately one-third, especially in the context of low transmission rates [30].…”

Section: Disease Presentation: Clinical Symptomsmentioning

confidence: 99%

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Epidemiology of Cutaneous Leishmaniasis in Tunisia

Bettaieb¹,

Nouira²

2017

The Epidemiology and Ecology of Leishmaniasis

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In Tunisia, Zoonotic cutaneous leishmaniasis (ZCL) represents the most significant leishmaniasis form. The epidemic of ZCL emerged in Central Tunisia in 1982 and expanded to the whole central and southern parts of the country. Tunisian ZCL is caused by Leishmania (L). major zymodeme MON-25 and transmitted by Phlebotomus papatasi. Rodents constitute the reservoir for ZCL. They include Psammomys obesus, Meriones shawi and Meriones libycus. ZCL occurs as seasonal epidemics and the annual incidence ranges from 2 to 10 thousand cases. Transmission of L. major by the phlebotomine sandfly vector occurs during the summer months, and active lesions in humans tend to emerge during the autumn and winter months. The symptoms of the disease are rather polymorphic, ranging from benign self-limited cutaneous sores to more protracted and extensive lesions that may cause severe disfigurement. Asymptomatic infection occurs frequently in endemic areas indicating a high level of immunity of the residents in these regions. The transmission of ZCL, its drastic increase and its spread are influenced by environmental changes affecting the reservoir and vector geographic distributions and by the lack of efficacy of the control tools available.

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“…Studies show that many individuals in cutaneous leishmaniasis endemic areas display strong leishmanin skin test (LST) and Leishmania-specific granzyme B reactivity (even in the absence of visible cutaneous lesions), strongly reflecting the presence of infection-induced immunity (12,13). Our primary goal was to investigate the effect of inoculating killed L. major into such individuals.…”

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confidence: 99%

Inoculation of killed Leishmania major into immune mice rapidly disrupts immunity to a secondary challenge via IL-10-mediated process

Okwor

Liu

Beverley

et al. 2009

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

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Recovery from natural or experimental Leishmania major infection, the causative agent of cutaneous leishmaniasis, results in development of durable immunity in mice and humans that is manifested as rapid control of parasite replication and resolution of cutaneous lesion after secondary challenge. This form of ''infection-induced'' immunity is thought to occur naturally in endemic areas and is generally considered the gold standard for any effective vaccine against cutaneous leishmaniasis. To determine factors that might heighten or abrogate infection-induced immunity, we investigated the impact of inoculating dead antigen in the form of killed Leishmania parasites to healed mice. We show that inoculation of killed parasites into mice that resolved their primary virulent L. major infection results in rapid and relatively sustained loss of infection-induced immunity. This loss of immunity was not due to the inability of killed parasites to induce inflammatory responses (such as delayed type hypersensitivity), but it was related to their failure to induce robust IFN-␥ response. Furthermore, inoculation of killed Leishmania parasites into healed mice led to rapid expansion of IL-10-producing CD4 ؉ CD25 ؉ Foxp3 ؉ T cells in lymph nodes draining the primary infection site. Treatment with anti-CD25 or anti-IL-10R mAb abolished killed parasiteinduced loss of immunity. Our study suggests that vaccination with killed parasites could predispose naturally immune individuals to become susceptible to new infections and/or disease reactivation. This may account for the lack of efficacy of such vaccines in field trials in endemic regions. These findings have important implications for vaccine design and vaccination strategies against human cutaneous leishmaniasis.parasitic-protozoa ͉ regulatory T cells ͉ vaccination ͉ cytokines ͉ memory E xperimental murine infection with Leishmania major has provided extensive information on the factors that regulate the development and maintenance of CD4 ϩ T-helper (Th) cells in vivo (1). However, there is still no effective vaccine against human cutaneous leishmaniasis. Several vaccination trials using heat-killed Leishmania parasites in humans have yielded disappointing results (2). In contrast, several experimental vaccines were effective in murine studies, many of them relying on IL-12 or components that induce IL-12, as adjuvants (3, 4). However, as with heat-killed human vaccines, the protection often wanes within a short period.Recovery from natural or experimental Leishmania major infections in humans and mice results in persistence of low numbers of parasites at the primary site of infection (5) and development of durable immunity (6, 7). IFN-␥-producing CD4 ϩ T cells (8, 9), whose maintenance is dependent on persistent live parasites (10, 11), mediate infection-induced immunity. Thus, infection-induced immunity is a gold standard of anti-Leishmania immunity that must be attained by any Leishmania vaccine to be considered effective (12). Therefore, understanding the factors that cont...

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The Predictive Validity of Naturally Acquired Delayed‐Type Hypersensitivity to Leishmanin in Resistance toLeishmania major–Associated Cutaneous Leishmaniasis

Cited by 36 publications

References 30 publications

Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due toLeishmania majorInfection in Four Inbred Mouse Strains

Comparative Evaluation of Two Vaccine Candidates against Experimental Leishmaniasis Due toLeishmania majorInfection in Four Inbred Mouse Strains

Epidemiology of Cutaneous Leishmaniasis in Tunisia

Inoculation of killed Leishmania major into immune mice rapidly disrupts immunity to a secondary challenge via IL-10-mediated process

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