Vaccination with Leishmania infantum Acidic Ribosomal P0 but Not with Nucleosomal Histones Proteins Controls Leishmania infantum Infection in Hamsters

Several intracellular Leishmania antigens have been identified in order to find a potential vaccine capable of conferring long lasting protection against Leishmania infection. Histones and Acid Ribosomal proteins are already known to induce an effective immune response and have successfully been tested in the cutaneous leishmaniasis mouse model. Here, we investigate the protective ability of L. infantum nucleosomal histones (HIS) and ribosomal acidic protein P0 (LiP0) against L. infantum infection in the hamster model of visceral leishmaniasis using two different strategies: homologous (plasmid DNA only) or heterologous immunization (plasmid DNA plus recombinant protein and adjuvant)Peer Reviewe

Clear cell sarcoma of the parotid region

UNIFESP-EPMUNIFESP-EPM Departamento de PatologiaUNIFESP-EPM Departamento de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoUNIFESP, EPM, Depto. de PatologiaUNIFESP, EPM Depto. de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoSciEL

New Insights on the Inflammatory Role of Lutzomyia longipalpis Saliva in Leishmaniasis

When an haematophagous sand fly vector insect bites a vertebrate host, it introduces its mouthparts into the skin and lacerates blood vessels, forming a hemorrhagic pool which constitutes an intricate environment of cell interactions. In this scenario, the initial performance of host, parasite, and vector “authors” will heavily influence the course of Leishmania infection. Recent advances in vector-parasite-host interaction have elucidated “co-authors” and “new roles” not yet described. We review here the stimulatory role of Lutzomyia longipalpis saliva leading to inflammation and try to connect them in an early context of Leishmania infection

Proteome Profiling of Human Cutaneous Leishmaniasis Lesion

In this study, we used proteomics and biological network analysis to evaluate the potential biological processes and components present in the identified proteins of biopsies from cutaneous leishmaniasis (CL) patients infected by Leishmania braziliensis in comparison with normal skin. We identified 59 proteins differently expressed in samples from infected and normal skin. Biological network analysis employing identified proteins showed the presence of networks that may be involved in the cell death mediated by cytotoxic T lymphocytes. After immunohistochemical analyses, the expression of caspase-9, caspase-3, and granzyme B was validated in the tissue and positively correlated with the lesion size in CL patients. In conclusion, this work identified differentially expressed proteins in the inflammatory site of CL, revealed enhanced expression of caspase-9, and highlighted mechanisms associated with the progression of tissue damage observed in lesions

Molecular Aspects of Dendritic Cell Activation in Leishmaniasis: An Immunobiological View

Dendritic cells (DC) are a diverse group of leukocytes responsible for bridging innate and adaptive immunity. Despite their functional versatility, DCs exist primarily in two basic functional states: immature and mature. A large body of evidence suggests that upon interactions with pathogens, DCs undergo intricate cellular processes that culminate in their activation, which is paramount to the orchestration of effective immune responses against Leishmania parasites. Herein we offer a concise review of the emerging hallmarks of DCs activation in leishmaniasis as well as a comprehensive discussion of the following underlying molecular events: DC-Leishmania interaction, antigen uptake, costimulatory molecule expression, parasite ability to affect DC migration, antigen presentation, metabolic reprogramming, and epigenetic alterations

Coinfection with Trypanosoma brucei confers protection against cutaneous leishmaniasis

Infection with certain bacteria, parasites, and viruses alters the host immune system to Leishmania major influencing disease outcome. Here, we determined the outcome of a chronic infection with Trypanosoma brucei brucei on cutaneous leishmaniasis (CL) caused by L. major. C57BL/6 mice infected with T. b. brucei were given a sub-curative treatment with diminazene aceturate then coinfected with L. major by vector bites. Our results revealed that infection with T. b. brucei controls CL pathology. Compared to controls, coinfected mice showed a significant decrease in lesion size (P < 0.05) up to 6 weeks post-infection and a significant decrease in parasite burden (P < 0.0001) at 3 weeks post-infection. Protection against L. major resulted from a non-specific activation of T cells by trypanosomes. This induced a strong immune response characterized by IFN-gamma production at the site of bites and systemically, creating a hostile inflammatory environment for L. major parasites and conferring protection from CL

Vaccination with Leishmania infantum Acidic Ribosomal P0 but Not with Nucleosomal Histones Proteins Controls Leishmania infantum Infection in Hamsters

Several intracellular Leishmania antigens have been identified in order to find a potential vaccine capable of conferring long lasting protection against Leishmania infection. Histones and Acid Ribosomal proteins are already known to induce an effective immune response and have successfully been tested in the cutaneous leishmaniasis mouse model. Here, we investigate the protective ability of L. infantum nucleosomal histones (HIS) and ribosomal acidic protein P0 (LiP0) against L. infantum infection in the hamster model of visceral leishmaniasis using two different strategies: homologous (plasmid DNA only) or heterologous immunization (plasmid DNA plus recombinant protein and adjuvant). Immunization with both antigens using the heterologous strategy presented a high antibody production level while the homologous strategy immunized group showed predominantly a cellular immune response with parasite load reduction. The pcDNA-LiP0 immunized group showed increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β in the lymph nodes before challenge. Two months after infection hamsters immunized with the empty plasmid presented a pro-inflammatory immune response in the early stages of infection with increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β, whereas hamsters immunized with pcDNA-HIS presented an increase only in the ratio IFN-γ/ TGF-β. On the other hand, hamsters immunized with LiP0 did not present any increase in the IFN-γ/TGF-β and IFN-γ/IL-10 ratio independently of the immunization strategy used. Conversely, five months after infection, hamsters immunized with HIS maintained a pro-inflammatory immune response (ratio IFN-γ/ IL-10) while pcDNA-LiP0 immunized hamsters continued showing a balanced cytokine profile of pro and anti-inflammatory cytokines. Moreover we observed a significant reduction in parasite load in the spleen, liver and lymph node in this group compared with controls. Our results suggest that vaccination with L. infantum LiP0 antigen administered in a DNA formulation could be considered a potential component in a vaccine formulation against visceral leishmaniasisThis study was funded by CNPq and CYTED. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Diferenças no perfil antigênico de tripomastigotas sangüícolas e de cultura celular do Trypanosoma cruzi

A comparative study of the antigenic profile of bloodstream and cell culture derived trypomastigotes showed many differences in their components. Using mouse anti-T. cruzi antibodies the differences were located mostly in the 120 kDa band, whereas using chagasic patient sera the differences were located in the 85 and 52 kDa bands. These findings might explain known physiological differences between trypomatigotes obtained from cell culture and from infected blood. A brief report of this work has already been published9.O estudo comparativo do perfil antigênico de tripomastigotas sangüícolas e tripomatigotas obtidos por cultura celular do Trypanosoma cruzi revelou que estas formas apresentam diferenças em alguns de seus componentes. Utilizando-se anticorpos provenientes da infecção murina, as diferenças foram detectadas na região de 120 kDa enquanto soros de pacientes chagásicos detectaram diferenças nas regiões de 85 e 52 kDa. Estas observações podem oferecer uma explicação a diferenças fisiológicas que ocorrem entre os tripomastigotas sangüícolas e os obtidos de cultura celular

Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11

Background: Vaccine development has been a priority in the fight against leishmaniases, which are vector-borne diseases caused by Leishmania protozoa. Among the different immunization strategies employed to date is inoculation of plasmid DNA coding for parasite antigens, which has a demonstrated ability to induce humoral and cellular immune responses. In this sense, inoculation of plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was able to confer protection against visceral leishmaniasis. However, recently the use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles has also proven effective for eliciting protective immune responses. Methods: In the present work, we tested two immunization strategies with the goal of obtaining protection, in terms of lesion development and parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP-11. Alternatively, mice were primed with PLGA nanoparticles loaded with the recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with recombinant KMP-11. Results: Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti-inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development was not inhibited following either immunization strategy. However, immunization with PLGA nanoparticles resulted in a more prominent reduction in parasite load at the infection site when compared with immunization using plasmid DNA alone. This effect was associated with a local increase in interferon-gamma and in tumor necrosis factor-alpha. Both immunization strategies also resulted in a lower parasite load in the draining lymph nodes, albeit not significantly. Conclusion: Our results encourage the pursuit of immunization strategies employing nanobased delivery systems for vaccine development against cutaneous leishmaniasis caused by L. braziliensis infection. © 2012 Santos et al, publisher and licensee Dove Medical Press Ltd.Government of Navarra; CAN Foundation and CYTEDPeer Reviewe