Fabíola Cardillo - Academia.edu (original) (raw)

Papers by Fabíola Cardillo

Immunology, Dec 1, 2007

In this study, we have evaluated the production of pro-and anti-inflammatory cytokines and the fo... more In this study, we have evaluated the production of pro-and anti-inflammatory cytokines and the formation of central and effector memory T cells in mice lacking mature B cells (muMT KO). The results show that Trypanosoma cruzi infection in C57Bl/6ml MT KO mice is intensified in relation to control mice and this exacerbation is related to low levels of inflammatory cytokines produced during the acute infection and the lower numbers of central and effector memory CD4 + and CD8 + T cells generated during the acute phase of the infection. In addition, a marked reduction in the CD8 + T-cell subpopulation was observed in muMT KO infected mice. In agreement to this, the degree of tissue parasitism was increased in muMT mice and the tissue inflammatory response was much less intense in the acute phase of the infection, consistent with a deficit in the generation of effector T cells. Flow cytometry analysis of the skeletal muscle inflammatory infiltrate showed a predominance of CD8 + CD45Rb low in B-cell-sufficient C57Bl/6 mice, whereas the preponderant cell type in muMT KO skeletal muscle inflammatory infiltrate was CD4 + T cells. In addition, CD8 + T cells found in skeletal muscle from muMT KO infected mice were less activated than in control B-cell sufficient infected mice. These results suggest that B cells may participate in the generation of effector/memory T cells. In addition and more importantly, B cells were crucial in the maintenance of central and effector memory CD8 + T cell, as well as the determination of the T cell cytokine functional pattern, and they may therefore account for critical aspects of the resistance to intracellular pathogens, such as T. cruzi.

PubMed, Aug 1, 2004

Background: This study evaluated the regulatory function of NK1.1+ cells during Trypanosoma cruzi... more Background: This study evaluated the regulatory function of NK1.1+ cells during Trypanosoma cruzi infection. Material/methods: Both thymectomized (Tx C57Bl/6) and euthymic C57Bl/6 mice (C57Bl/6) were infected intraperitoneally with the Tulahuen strain. NK1.1+ cells were depleted in vivo by anti-NK1.1 mAb. Spleen cells were analyzed by flow cytometry for the expression of CD44 and CD69 on T cells. Supernatants from splenocytes were used to measure nitrite concentration (quantified by Griess reagent). Interleukin 2 and IFN-gamma levels were determined by ELISA. The protocols used herein were approved by the Institutional Committee for Ethics. Student's t or Kruskal-Wallis tests were applied, as indicated. Results: The number of T cells expressing CD69 increased progressively during T. cruzi infection in NK1.1 cell-depleted C57Bl/6 mice. In spite of an increased early T cell activation during infection, the percentage of CD4+ CD44high T cells did not augment in NK1.1 cell-depleted C57Bl/6 mice compared with untreated C57Bl/6 controls. Serum levels of IFN-gamma in anti-NK1.1-treated mice were higher than in non-depleted animals. Con-A-stimulated spleen cell supernatants from NK1.1 cell-depleted animals contained increased levels of IL-2 and nitric oxide (NO) during early infection. Conclusions: After the first week of infection, NO overproduction and high levels of IFN-gamma in anti-NK1.1-tre-ated C57Bl/6 mice appeared to be related to susceptibility and hyperactivation of peripheral T cells. Finally, this study suggests a novel regulatory function of NK1.1+ cells during T. cruzi infection. Without NK1.1 cells, T lymphocytes are hyperactivated but do not differentiate to effector/memory T cells in infected C57Bl/6 mice.

Iubmb Life, Mar 1, 1997

The Soret region absorption spectrum of erythrocruorin (ERC) obtained from Glossoscolex paulis... more 1) The Soret region absorption spectrum of erythrocruorin (ERC) obtained from Glossoscolex paulistus, shows that oxy-ERC has a maximum absorption peak at 416 nm while the deoxy-ERC from has a maximum at 427 nm. 2) In the presence of a specific antiserum (anti-ERC) and of anti-ERC immunoglobulin G raised in rabbits, there is a deviation to low wavelengths in the maximum absorption peak of deoxy-ERC while for the oxy form a red-shift is noticed. These shifts accompanied an increased affinity of the hemeprotein for oxygen, possibly because of changes in the overall macromolecular conformation. 3) A decrease in the oxygen affinity of erythrocruorin is observed when large amounts of non-specific serum are used. The same effect is observed in the presence of serum albumin, probably as a result of non-specific binding between the albumin and erythrocruorin. 4) The fluorimetric titration of erythrocruorin with anti-ERC Fab fragments results in a decrease in the intrinsic tryptophan fluorescence of the hemeprotein, a response indicative of a modification in the ERC&amp;amp;amp;#39;s quaternary structure.

Immunology, Oct 1, 2005

We show, here, that one single injection or weekly injections of staphylococcal enterotoxin B (SE... more We show, here, that one single injection or weekly injections of staphylococcal enterotoxin B (SEB), starting in 1-day-old newborn mice, induced a powerful immune response with a T helper type 2 (Th2) pattern, as judged by the isotype and cytokine profile, with the production of large amounts of SEB-specific immunoglobulin G1 (IgG1), detectable levels of SEB-specific IgE and increased production of interleukin-4 by spleen cells. These protocols also induced an increase in the levels of total IgE in the serum. Memory of SEB was transferred to secondary recipients by using total spleen cells from primed animals. The secondary humoral response in transferred mice was diminished if spleen cells from SEB-treated mice were previously depleted of CD3 + or Vb8 + T cells or NK1.1 + cells. In vivo depletion of NK1.1 + cells in adult mice resulted in a marked reduction in the SEB-specific antibody response in both the primary and secondary immune responses. Additionally, purified NK1.1 + T cells were able to perform SEB-specific helper B-cell actions in vitro and in vivo. These results suggest that NK1.1 + T cells are required for the full development of humoral immunological memory, whilst making neonatal tolerance to SEB unachievable.

Um importante fator de virulência e modulador da infectividade do Trypanosoma cruzi é a NTPDase-1... more Um importante fator de virulência e modulador da infectividade do Trypanosoma cruzi é a NTPDase-1, uma ectonucleotidase da sub-família E-NTPDase presente na superfície deste parasito, responsável por hidrolisar e regular a sinalização purinérgica mediada por nucleotídeos extracelulares. A influência da atividade das ENTPDases, como a NTPDase-1, na infecção e virulência da cepa Y do T. cruzi, foi demonstrado que a inibição enzimática leva a uma redução da infecção in vitro; bem como a atenuação da virulência em modelo murino. O objetivo deste estudo foi avaliar o papel das ectonucleotidases na forma tripomastigota metacíclica da cepa Colombiana (“discrete typing unit” DTU I) do T. cruzi na fase aguda da infecção experimental. Para isso, ensaios in vitro e in vivo (protocolo CEUA 2016/29) foram propostos: mensuração da atividade das ectonucleotidases das formas tripomastigotas metacíclicas; infecção de camundongos C57BL/6 com 1x103 formas tripomastigotas metacíclicas pré-tratadas ou n...

Immunology Letters, Sep 1, 2022

Frontiers in Immunology, Jan 28, 2022

Chagas disease is accompanied by a multisystem inflammatory disorder that follows Trypanosoma cru... more Chagas disease is accompanied by a multisystem inflammatory disorder that follows Trypanosoma cruzi infection. Alpha-tocopherol has been described as an antioxidant and a potential adjuvant to enhance immune responses to vaccines. Therefore, we have evaluated the immune response to T. cruzi infection upon alpha-tocopherol preadministration. The results show that administration of alpha-tocopherol before the infection results in lower parasitemia and lower mortality of C57BL/6 mice infected with the Tulahuen T. cruzi strain. Alpha-tocopherol administration in normal C57BL/6 mice resulted in higher levels of IFN-g production by T and NK cells before and after the infection with T. cruzi. More importantly, previous administration of alpha-tocopherol increased the production of IL-10 by T and myeloid suppressor cells and the formation of effector memory T cells while decreasing the expression of PD-1 on T cells. These results suggest that alpha-tocopherol may limit the appearance of dysfunctional T cells during the acute and early chronic phases of T. cruzi infection, contributing to control infection. In addition, alpha-tocopherol could diminish tissue inflammation and fibrosis in late acute disease. These results strongly suggest that alpha-tocopherol may be a helpful agent to be considered in Chagas disease.

Frontiers in Microbiology, May 13, 2016

Scandinavian Journal of Immunology, 2002

Natural killer (NK) cells may provide the basis for resistance to Trypanosoma cruzi infection, be... more Natural killer (NK) cells may provide the basis for resistance to Trypanosoma cruzi infection, because the depletion of NK1.1 cells causes high levels of parasitemia in young C57Bl/6 mice infected with T. cruzi. Indeed, NK1.1 cells have been implicated in the early production of large amounts of interferon (IFN)-g, an important cytokine in host resistance. The NK1.1 marker is also expressed on special subpopulations of T cells. Most NK1.1 T cells are of thymic origin, and their constant generation may be prevented by thymectomy. This procedure, by itself, decreased parasitemia and increased resistance in young mice. However, the depletion of NK1.1 cells by the chronic administration of a monoclonal antibody (MoAb) (PK-136) did not increase the parasitemia or mortality in thymectomized C57Bl/6 mice infected with T. cruzi (Tulahuen strain). To study the cross-talk between NK1.1 cells and conventional T cells in this model, we examined the expression of activation/memory markers (CD45RB) on splenic CD4 and CD8 T cells from young euthymic or thymectomized mice with or without depletion of NK1.1 cells and also in aged mice during acute infection. Resistance to infection correlated with the amount of CD4 T cells that are already activated at the moment of infection, as judged by the number of splenic CD4 T cells expressing CD45RB ±. In addition, the specific antibody response to T. cruzi antigens was precocious and an accumulation of immunoglobulin (Ig)M with little isotype switch occurred in euthymic mice depleted of NK1.1 cells. The data presented here suggest that NK1.1 cells have important regulatory functions in euthymic, but not in thymectomized mice infected with T. cruzi. These regulatory functions include a helper activity in the generation of effector or activated/memory T cells.

International Immunology, Feb 1, 1998

We have previously shown that splenic γδ T cells from young but not aged BALB/c mice possess supp... more We have previously shown that splenic γδ T cells from young but not aged BALB/c mice possess suppressor activity in vivo and in vitro during the acute phase of Trypanosoma cruzi infection. The present work was undertaken to investigate the suppressor activity of γδ T cells from T. cruziinfected euthymic or athymic mice and the role of the thymus in modulating non-adherent spleen cell suppressor activity during the acute phase of infection. Splenic γδ T cells from aged or athymic BALB/c mice reconstituted with total spleen cells or non-reconstituted did not exhibit suppressor activity when added to full allogeneic, mixed lymphocyte cultures. In contrast, splenic γδ T cells from young euthymic BALB/c mice showed suppressor activity in vitro. Thymectomy reduced the splenic γδ T cell suppressor activity of young BALB/c mice in a time-dependent manner, following a T. cruzi challenge. The continuous provision of thymocytes to aged mice, young thymectomized mice or total spleen cell-reconstituted athymic mice could re-establish the γδ T cell suppressor activity. Of particular significance was the observation that the depletion of γδ T cells during the acute phase of T. cruzi infection restored the capacity of these mice to mount a humoral immune response to a non-related antigen such as ovalbumin. These results indicate that γδ T cells of extrathymic origin cannot mediate suppression and that the thymus has a role in the regulation of suppression during the acute phase of T. cruzi infection.

Pathogens and Disease, Oct 4, 2015

This article reviews the immune mechanisms responsible for the control of parasite numbers as wel... more This article reviews the immune mechanisms responsible for the control of parasite numbers as well as the mechanisms that control the immune response, avoiding tissue damage and disease.

Microbes and Infection, Mar 1, 2006

Many different cell populations or lineages participate in the resistance to Trypanosoma cruzi in... more Many different cell populations or lineages participate in the resistance to Trypanosoma cruzi infection. gd T cells may also take part in a network of interactions that lead to control of T. cruzi infection with minimal tissue damage by controlling ab T cell activation, as was previously suggested. However, the gd T cell population is not homogeneous and its functions might vary, depending on T cell receptor usage or distinct stimulatory conditions. In this study, we show that the in vivo depletion of Vg1-bearing gd T cells, prior to the infection of BALB/c mice with the Y strain of T. cruzi, induces an increased susceptibility to the infection with lower amounts of IFN-g being produced by conventional CD4þ or CD8þ T cells. In addition, the production of IL-4 by spleen T cells in Vg1-depleted mice was increased and the production of IL-10 remained unchanged. Since Vg1 þ gd T cell depletion diminished the conversion of naive to memory/activated CD4 T cells and the production of IFN-g during the acute infection, these cells appear to function as helper cells for conventional CD4þ Th1 cells. Depletion of Vg1 þ cells also reduced the infection-induced inflammatory infiltrate in the heart and skeletal muscle. More importantly, Vg1 þ cells were required for up-regulation of CD40L in CD4þ and CD8þ T cells during infection. These results show that a subset of gd T cells (Vg1 þ), which is an important component of the innate immune response, up-regulates the type 1 arm of the adaptative immune response, during T. cruzi infection.

Frontiers in Immunology, Aug 11, 2016

Vaccines, May 1, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY