Publications by authors named "Paula M de Luca"

8 Publications

  • Page 1 of 1

Tregs in the immune response of BALB/c mice experimentally infected with species of the genus.

Future Microbiol 2020 09;15:1217-1225

Laboratory of Clinical Research in Dermatozoonosis in Domestic Animals, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.

Sporotrichosis occurs through contact with contaminated soil and plant. However, the incidence of sporotrichosis as a zoonotic epidemic has increased, particularly in Rio de Janeiro. In this work, we decided to evaluate some T-cell phenotypes involved in the immune response. We used flow cytometry to quantify TCD4 and TCD8 and Treg from immunocompetent and immunosuppressed mice infected with species with different levels of virulence and pathogenicity. It was demonstrated the predominance of TCD4 over the TCD8 cells in both groups, inoculated with all the species, and percentages of Treg observed in infected immunocompetent mice. This regulatory phenotype can be associated with a protective immunity in the initial periods of infection.
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http://dx.doi.org/10.2217/fmb-2020-0046DOI Listing
September 2020

Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon.

Immun Inflamm Dis 2018 06 3;6(2):207-220. Epub 2018 Jan 3.

Laboratory of Clinical Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Avenida Brasil 4365, Manguinhos, Rio de Janeiro, RJ, Brazil, 21040-360.

Introduction: A proliferation-inducing ligand (APRIL) and B cell activation factor (BAFF) are known to play a significant role in the pathogenesis of several diseases, including BAFF in malaria. The aim of this study was to investigate whether APRIL and BAFF plasma concentrations could be part of inflammatory responses associated with P. vivax and P. falciparum malaria in patients from the Brazilian Amazon.

Methods: Blood samples were obtained from P. vivax and P. falciparum malaria patients (n = 52) resident in Porto Velho before and 15 days after the beginning of treatment and from uninfected individuals (n = 12). We investigated APRIL and BAFF circulating levels and their association with parasitaemia, WBC counts, and cytokine/chemokine plasma levels. The expression levels of transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) on PBMC from a subset of 5 P. vivax-infected patients were analyzed by flow cytometry.

Results: APRIL plasma levels were transiently increased during acute P. vivax and P. falciparum infections whereas BAFF levels were only increased during acute P. falciparum malaria. Although P. vivax and P. falciparum malaria patients have similar cytokine profiles during infection, in P. vivax acute phase malaria, APRIL but not BAFF levels correlated positively with IL-1, IL-2, IL-4, IL-6, and IL-13 levels. We did not find any association between P. vivax parasitaemia and APRIL levels, while an inverse correlation was found between P. falciparum parasitaemia and APRIL levels. The percentage of TACI positive CD4+ and CD8+ T cells were increased in the acute phase P. vivax malaria.

Conclusion: These findings suggest that the APRIL and BAFF inductions reflect different host strategies for controlling infection with each malaria species.
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http://dx.doi.org/10.1002/iid3.208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946147PMC
June 2018

Experimental Hyalohyphomycosis by Outcome of the Infection in C57BL/6 Murine Models.

Front Microbiol 2017 23;8:1617. Epub 2017 Aug 23.

Laboratory of Taxonomy, Biochemistry and Bioprospecting of Fungi, Oswaldo Cruz Institute, Oswaldo Cruz FoundationRio de Janeiro, Brazil.

is a filamentous, hyaline fungus considered an emerging pathogen in humans. The aim of our study was to evaluate the outcome of hyalohyphomycosis in C57BL/6 murine models inoculated with two clinical isolates (S1 and S2). Each isolate was inoculated in mice randomly distributed in immunocompetent (CPT) and immunosuppressed (SPS) groups. Mice were evaluated at day 7, 21, and 45 after inoculation for histopathological analysis, recovery of fungal cells, and immunological studies. Histological analysis showed scarce conidia-like structures in lung tissue from CPT mice and a lot of fungal cells in SPS mice inoculated with S2 compared to mice inoculated with S1. The maximum recovery of fungal cells was seen in CPT mice inoculated with both isolates at day 7, but with mean significantly higher in those inoculated with S2 isolate. Phenotypical characterization of T cells showed TCD8 lymphocytes predominance over TCD4 in immunosuppressed mice infected and control groups. We also observed higher percentages of the central and effector memory/effector phenotype in CPT mice infected with S2 strain, especially in TCD8 in the initial period of infection. Regulatory T cells showed higher percentages in immunosuppressed, predominantly after the acute phase. Our results showed that the is a fungus capable to cause damages in competent and immunosuppressed experimental hosts. Furthermore, S2 isolate seems to cause more damage to the experimental host and it was possible to identify different cellular subsets involved in the mice immune response.
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http://dx.doi.org/10.3389/fmicb.2017.01617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572354PMC
August 2017

F1 Domain of the Nucleoside Hydrolase Promotes a Th1 Response in Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis.

Front Immunol 2017 12;8:750. Epub 2017 Jul 12.

Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

The nucleoside hydrolase NH36 is the main antigen of the Leishmune vaccine and one of the promising candidates for vaccination against visceral leishmaniasis. The antigenicity of the N-terminal (F1), the central (F2), or the C-terminal recombinant domain (F3) of NH36 was evaluated using peripheral blood mononuclear cells (PBMC) from individuals infected with from an endemic area of visceral leishmaniasis of Spain. Both NH36 and F1 domains significantly increased the PBMC proliferation stimulation index of cured patients and infected asymptomatic individuals compared to healthy controls. Moreover, F1 induced a 19% higher proliferative response than NH36 in asymptomatic exposed subjects. In addition, in patients cured from visceral leishmaniasis, proliferation in response to NH36 and F1 was accompanied by a significant increase of IFN-γ and TNF-α secretion, which was 42-43% higher, in response to F1 than to NH36. The interleukin 17 (IL-17) secretion was stronger in asymptomatic subjects, in response to F1, as well as in cured cutaneous leishmaniasis after NH36 stimulation. While no IL-10 secretion was determined by F1, a granzyme B increase was detected in supernatants from cured patients after stimulation with either NH36 or F1. These data demonstrate that F1 is the domain of NH36 that induces a recall cellular response in individuals with acquired resistance to the infection by . In addition, F1 and NH36 discriminated the IgG3 humoral response in patients with active visceral leishmaniasis due to (Ethiopia) and (Spain) from that of endemic and non-endemic area controls. NH36 showed higher reactivity with sera from -infected individuals, indicating species specificity. We conclude that the F1 domain, previously characterized as an inducer of the Th1 and Th17 responses in cured/exposed patients infected with , may also be involved in the generation of a protective response against and represents a potential vaccine candidate for the control of human leishmaniasis alone, or in combination with other HLA epitopes/antigens.
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http://dx.doi.org/10.3389/fimmu.2017.00750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506215PMC
July 2017

Malaria-Cutaneous Leishmaniasis Co-infection: Influence on Disease Outcomes and Immune Response.

Front Microbiol 2016 27;7:982. Epub 2016 Jun 27.

Laboratory of Simulids, Onchocerciasis and Sympatric Diseases: Mansonelliasis and Malaria, Oswaldo Cruz Institute, Oswaldo Cruz Foundation Rio de Janeiro, Brazil.

Malaria and Cutaneous Leishmaniasis (CL) are co-endemic throughout large regions in tropical countries and co-infection may impact the evolution of host-parasite interactions. In the present study, we evaluate Malaria/Leishmaniasis disease outcome, Th1/Th2 cytokine levels and the CD4 and CD8 T-cell profiles in a co-infection murine model (BALB/c) of Plasmodium yoelii 17XNL (Py) and Leishmania amazonensis (La) or L. braziliensis (Lb). Malaria parasitaemia was assessed through blood strains stained with Giemsa. Leishmania lesions were monitored with a digital caliper and parasite loads determined by limiting-dilution assay. Serum levels of IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10, and IL-17 were determined using multiplexed bead assay and expression of CD3, CD4, and CD8 T-cells markers were determined by Flow Cytometry in the thymus, spleens and lymph nodes. Parasitaemia in Lb+Py co-infected group was lower than in Py single-infected group, suggesting a protective effect of Lb co-infection in Malaria progression. In contrast, La+Py co-infection increased parasitaemia, patent infection and induced mortality in non-lethal Malaria infection. Regarding Leishmaniasis, Lb+Py co-infected group presented smaller lesions and less ulceration than Lb single-infected animals. In contrast, La+Py co-infected group presented only a transitory delay on the development of lesions when compared to La single-infected mice. Decreased levels of IFN-γ, TNF, IL-6, and IL-10 were observed in the serum of co-infected groups, demonstrating a modulation of Malaria immune response by Leishmania co-infections. We observed an intense thymic atrophy in Py single-infected and co-infected groups, which recovered earlier in co-infected animals. The CD4 and CD8 T cell profiles in thymus, spleens and lymph nodes did not differ between Py single and co-infected groups, except for a decrease in CD4(+)CD8(+) T cells which also increased faster in co-infected mice. Our results suggest that Py and Leishmania co-infection may change disease outcome. Interestingly Malaria outcome can be altered according to the Leishmania specie involved. Alternatively Malaria infection reduced the severity or delayed the onset of leishmanial lesions. These alterations in Malaria and CL development seem to be closely related with changes in the immune response as demonstrated by alteration in serum cytokine levels and thymus/spleens T cell phenotypes dynamics during infection.
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http://dx.doi.org/10.3389/fmicb.2016.00982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921482PMC
July 2016

Detection of antibody to Purpureocillium lilacinum by immunofluorescent assay and flow cytometry in serum of infected C57BL/6 mice.

J Immunol Methods 2013 Oct 19;396(1-2):147-51. Epub 2013 Jul 19.

Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil; Laboratório de Imunologia Clínica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.

Purpureocillium lilacinum is an emerging pathogenic fungus that can cause different clinical manifestations ranging from cutaneous and sub-cutaneous infections to severe oculomycosis. In this study, using both conventional indirect immunofluorescence and non-conventional flow cytometry approaches, IgG antibodies were readily detected in both C57BL/6 immunocompetent and immunosuppressed mice after i.v. infection with P. lilacinum. The humoral immune response was specific, since virtually no antibodies were detected in the serum of control mice. Flow cytometry assays also showed both quantitative and qualitative differences in total IgG and its isotypes in sera of immunocompetent and immunosupressed infected mice. Although a good starting point, it is clear that the effectiveness of serological assays for P. lilacinum hyalohyphomycosis identification in clinical studies still requires further standardization. Upon further validation in humans, these techniques have the potential to be suitable to detect P. lilacinum infection in patients, thereby avoiding current laborious and time-consuming culture techniques.
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http://dx.doi.org/10.1016/j.jim.2013.07.002DOI Listing
October 2013

Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major.

Nat Med 2007 Jul 10;13(7):843-50. Epub 2007 Jun 10.

Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), 40 Convent Drive, Bethesda, Maryland 20892, USA.

CD4+ T cells have a crucial role in mediating protection against a variety of pathogens through production of specific cytokines. However, substantial heterogeneity in CD4+ T-cell cytokine responses has limited the ability to define an immune correlate of protection after vaccination. Here, using multiparameter flow cytometry to assess the immune responses after immunization, we show that the degree of protection against Leishmania major infection in mice is predicted by the frequency of CD4+ T cells simultaneously producing interferon-gamma, interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells generated by all vaccines tested are unique in their capacity to produce high amounts of interferon-gamma. These data show that the quality of a CD4+ T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (TH1) cells.
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http://dx.doi.org/10.1038/nm1592DOI Listing
July 2007

Leishmania (Leishmania) amazonensis-induced cutaneous leishmaniasis in the primate Cebus apella: a model for vaccine trials.

Int J Parasitol 2002 Dec;32(14):1755-64

Seção de Parasitologia, Programa de Imunologia, Instituto Evandro Chagas, Fundação Nacional de Sáude, Ministério da Saúde-BR 316, Km 7 S/N, CEP 67.030-070, Ananindeua, PA, Brazil.

A primate model of leishmaniasis was developed with the objective of future vaccine testing. Lesion development and immunological parameters were studied upon primary and secondary infections. Seven Cebus apella were injected subcutaneously with 2 x 10(6) Leishmania (Leishmania) amazonensis promastigotes. Erythematous nodules appeared 19-29 days p.i., which disappeared 100 days p.i. Four months later, six of the monkeys were challenged with the same inoculum; three of them developed erythematous nodules after 7 days p.i., with ulcer formation in two of these subjects. The lesions were short-lived and all were cured 40 days post challenge. Anti-Leishmania IgG antibodies were detected and they increased after the challenge infection. Leishmania antigen-induced lymphoproliferation was found 1 month post-primary infection, which coincided with IFN-gamma production and lesion development. It decreased to control levels afterwards, but at the time of the challenge dose, it was significantly above the initial level. After the challenge infection, it first increased then decreased sharply at 40 days post-challenge, coinciding with the healing of the lesion. It increased again to a higher level at 60 days post-challenge. Leishmania (Leishmania) amazonensis-infection in C. apella did not induce complete protection against a secondary infection with a homologous parasite although specific antibody production and lymphoproliferation with IFN-gamma production were observed. This fact indicates that vaccine has to be better than infection in the induction of protective immunity, and raises a question on in vitro parameters that should be considered as a counterpart of expected protection induced by vaccine candidate. In addition, we conclude that this is a useful primate model for the evaluation of candidate vaccines.
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http://dx.doi.org/10.1016/s0020-7519(02)00138-8DOI Listing
December 2002
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