Cloning of Genes and Expression and Antigenicity Analysis of theLeishmania infantumKMP-11 Protein

Berberich, Christof; Requena, José Marı́a; Alonso, Carlos

doi:10.1006/expr.1996.4120

Cited by 40 publications

(49 citation statements)

References 11 publications

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“…A second, minor immunoreactive band of 22 kDa, recognised by the anti-KMP-11 antibody in the recombinant KMP-11 preparation (Fig. 4B), is a dimeric form of the protein (Berberich et al 1997, Ramírez et al 1998. Taken together, the results presented in Fig.…”

Section: Kmp-11 Is Released In the Supernatant Of L Amazonensis-infesupporting

confidence: 61%

Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages

Lacerda

Cysne-Finkelstein

Nunes

et al. 2012

Mem. Inst. Oswaldo Cruz

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In Leishmania amazonensis, kinetoplastid membrane protein-11 (KMP-11) expression increases during metacyclogenesis and is higher in amastigotes than in promastigotes, suggesting a role for this protein in the infection of the mammalian host. We show that the addition of KMP-11 exacerbates L. amazonensis infection in peritoneal macrophages from BALB/c mice by increasing interleukin (IL)-10 secretion and arginase activity while reducing nitric oxide (NO) production. The doses of KMP-11, the IL-10 levels and the intracellular amastigote loads were strongly, positively and significantly correlated. The increase in parasite load induced by KMP-11 was inhibited by anti-KMP-11 or anti-IL-10 neutralising antibodies, but not by isotype controls. The neutralising antibodies, but not the isotype controls, were also able to significantly decrease the parasite load in macrophages cultured without the addition of KMP-11, demonstrating that KMP-11-induced exacerbation of the infection is not dependent on the addition of exogenous KMP-11 and that the protein naturally expressed by the parasite is able to promote it. In this study, the exacerbating effect of KMP-11 on macrophage infection with Leishmania is for the first time demonstrated, implicating it as a virulence factor in L. amazonensis. The stimulation of IL-10 production and arginase activity and the inhibition of NO synthesis are likely involved in this effect

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Section: Kmp-11 Is Released In the Supernatant Of L Amazonensis-infesupporting

confidence: 61%

Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages

Lacerda

Cysne-Finkelstein

Nunes

et al. 2012

Mem. Inst. Oswaldo Cruz

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“…23,24 Seropositivity against rTRYP was also significant because it was detected in half of the dogs studied, as found elsewhere. 23 When the two recombinant antigen-based ELISAs were evaluated in parallel, 80% of dogs with leishmaniasis showed seroreactvity against rKMPII or rTRYP.…”

Section: Discussionsupporting

confidence: 81%

Dynamics and Predictive Potential of Antibodies against Insect-Derived Recombinant Leishmania infantum Proteins during Chemotherapy of Naturally Infected Dogs

Todolí

Galindo²,

Gómez-Sebastián³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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“…The KMP-11 open reading frame of L. major was amplified by PCR using oligonucleotide primers (CB1 and CB2) which have been shown previously to be highly specific for the amplification of KMP-11 from genomic Leishmania DNA (35). The amplified 0.3-kb fragment was introduced, in frame, into pQE30.…”

Section: Cloning Recombinant Expression and Purification Of Leishmamentioning

confidence: 99%

Dendritic Cell (DC)-Based Protection Against an Intracellular Pathogen Is Dependent Upon DC-Derived IL-12 and Can Be Induced by Molecularly Defined Antigens

Berberich

Ramírez-Pineda

Hambrecht

et al. 2003

The Journal of Immunology

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110

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Upon loading with microbial Ag and adoptive transfer, dendritic cells (DC) are able to induce immunity to infections. This offers encouragement for the development of DC-based vaccination strategies. However, the mechanisms underlying the adjuvant effect of DC are not fully understood, and there is a need to identify Ag with which to arm DC. In the present study, we analyzed the role of DC-derived IL-12 in the induction of resistance to Leishmania major, and we evaluated the protective efficacy of DC loaded with individual Leishmania Ag. Using Ag-pulsed Langerhans cells (LC) from IL-12-deficient or wild-type mice for immunization of susceptible animals, we showed that the inability to release IL-12 completely abrogated the capacity of LC to mediate protection against leishmaniasis. This suggests that the availability of donor LC-derived IL-12 is a requirement for the development of protective immunity. In addition, we tested the protective effect of LC loaded with Leishmania homolog of receptor for activated C kinase, gp63, promastigote surface Ag, kinetoplastid membrane protein-11, or Leishmania homolog of eukaryotic ribosomal elongation and initiation factor 4a. The results show that mice vaccinated with LC that had been pulsed with selected molecularly defined parasite proteins are capable of controlling infection with L. major. Moreover, the protective potential of DC pulsed with a given Leishmania Ag correlated with the level of their IL-12 expression. Analysis of the cytokine profile of mice after DC-based vaccination revealed that protection was associated with a shift toward a Th1-type response. Together, these findings emphasize the critical role of IL-12 produced by the sensitizing DC and suggest that the development of a DC-based subunit vaccine is feasible.

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Cloning of Genes and Expression and Antigenicity Analysis of theLeishmania infantumKMP-11 Protein

Cited by 40 publications

References 11 publications

Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages

Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages

Dynamics and Predictive Potential of Antibodies against Insect-Derived Recombinant Leishmania infantum Proteins during Chemotherapy of Naturally Infected Dogs

Dendritic Cell (DC)-Based Protection Against an Intracellular Pathogen Is Dependent Upon DC-Derived IL-12 and Can Be Induced by Molecularly Defined Antigens

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