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dc.contributor.authorGarde, Esther
dc.contributor.authorRamirez, Laura
dc.contributor.authorCorvo, Laura
dc.contributor.authorSolana, Jose C.
dc.contributor.authorElena Martin, M.
dc.contributor.authorGonzález, Victor M
dc.contributor.authorGomez-Nieto, Carlos
dc.contributor.authorBarral, Aldina
dc.contributor.authorBarral-Netto, Manoel
dc.contributor.authorRequena, Jose M.
dc.contributor.authorIborra, Salvador 
dc.contributor.authorSoto, Manuel
dc.identifier.citationFront Cell Infect Microbiol. 2018; 8:112
dc.description.abstractDifferent members of intracellular protein families are recognized by the immune system of the vertebrate host infected by parasites of the genus Leishmania. Here, we have analyzed the antigenic and immunogenic properties of the Leishmania eIF2 and eIF2B translation initiation factors. An in silico search in Leishmania infantum sequence databases allowed the identification of the genes encoding the alpha, beta, and gamma subunits and the alpha, beta, and delta subunits of the putative Leishmania orthologs of the eukaryotic initiation factors F2 (LieIF2) or F2B (LieIF2B), respectively. The antigenicity of these factors was analyzed by ELISA using recombinant versions of the different subunits. Antibodies against the different LieIF2 and LieIF2B subunits were found in the sera from human and canine visceral leishmaniasis patients, and also in the sera from hamsters experimentally infected with L. infantum. In L. infantum (BALB/c) and Leishmania major (BALB/c or C57BL/6) challenged mice, a moderate humoral response against these protein factors was detected. Remarkably, these proteins elicited an IL-10 production by splenocytes derived from infected mice independently of the Leishmania species employed for experimental challenge. When DNA vaccines based on the expression of the LieIF2 or LieIF2B subunit encoding genes were administered inmice, an antigen-specific secretion of IFN-gamma and IL-10 cytokines was observed. Furthermore, a partial protection against murine CL development due to L. major infection was generated in the vaccinated mice. Also, in this work we show that the LieIF2 alpha subunit and the LieIF2B beta and delta subunits have the capacity to stimulate IL-10 secretion by spleen cells from naive mice. B-lymphocytes were identified as the major producers of this anti-inflammatory cytokine. Taking into account the data found in this study, it may be hypothesized that these proteins act as virulence factors implicated in the induction of humoral responses as well as in the production of the down-regulatory IL-10 cytokine, favoring a pathological outcome. Therefore, these proteins might be considered markers of disease.
dc.description.sponsorshipThe research made for this study was supported in Spain by grants from Ministerio de Ciencia e Innovacion FISPI14/00366 and FISPI14/00366 (FEDER FUNDING) and the Fondo de Investigaciones Sanitarias (ISCIII-RETICRD16/0027/0008-FEDER). A Brazilian grant from CNPq within the Ciencia sem Fronteiras-PVE program (Ref: 300174/2014-4) is also acknowledged. SI is funded by grant SAF2015-74561-JIN (FEDER FUNDING) by the Spanish Ministerio de Economia y Competitividad. Finally, Institutional grants from the Fundacion Ramon Areces and Banco de Santander to the CBMSO are also acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.publisherFrontiers Media 
dc.subjectVisceral leishmaniasis
dc.subjectTranslation initiation factors
dc.subjectExperimental murine models
dc.titleAnalysis of the Antigenic and Prophylactic Properties of the Leishmania Translation Initiation Factors eIF2 and eIF2B in Natural and Experimental Leishmaniasis
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderFundación Ramón Areces 
dc.contributor.funderBanco Santander 
dc.identifier.journalFrontiers in Cellular and Infection Microbiology
dc.repisalud.orgCNICCNIC::Grupos de investigación::Inmunobiología
dc.rights.accessRightsopen accesses_ES

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