Karina R Bortoluci

Karina R Bortoluci
Universidade Federal de São Paulo | UNIFESP · Center of Celular and Molecular Therapy

PhD

About

50
Publications
10,375
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Introduction
The main focus of my lab is understanding the molecular basis of innate immune recognition by using the experimental models of Salmonella typhimurium and Trypanosoma cruzi infections.
Additional affiliations
August 2008 - present
Universidade Federal de São Paulo
February 1998 - July 2008
University of São Paulo

Publications

Publications (50)
Article
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Annexin A1 (AnxA1) is a potent anti-inflammatory protein that downregulates proinflammatory cytokine release. This study evaluated the role of AnxA1 in the regulation of NLRP3 inflammasome activation and lipid release by starch-elicited murine peritoneal macrophages. C57bl/6 wild-type (WT) and AnxA1-null (AnxA1-/-) mice received an intraperitoneal...
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Although CD4+ Foxp3+ T cells are largely described in the regulation of CD4+ T cell responses, their role in the suppression of CD8+ T cell priming is much less clear. Because the induction of CD8+ T cells during experimental infection with Trypanosoma cruzi is remarkably delayed and suboptimal, we raised the hypothesis that this protozoan parasite...
Article
Background: Renal cell carcinoma (RCC) is a highly vascularized cancer resistant to chemotherapy and radiotherapy. RCC is frequently infiltrated with immune cells, with macrophages being the most abundant cell type. Alternatively activated M2 macrophages are known to contribute to tumor progression. Endostatin (ES) is a fragment of collagen XVIII...
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Tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop niche-specific funct...
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Neuronal apoptosis inhibitory protein (NAIP)/NOD-like receptor (NLR) containing a caspase activating and recruitment domain (CARD) 4 (NLRC4) inflammasome complexes are acti-vated in response to proteins from virulent bacteria that reach the cell cytosol. Specific NAIP proteins bind to the agonists and then physically associate with NLRC4 to form an...
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The purinergic P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine production and cell death. To investigate whether the innate immune response to damage signals could contribute to the development of pulmonary necrotic lesions in severe...
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Over the past 20 years, the immune effector mechanisms involved in the control of Trypanosoma cruzi , as well as the receptors participating in parasite recognition by cells of the innate immune system, have been largely described. However, the main questions on the physiopathology of Chagas disease remain unanswered: “Why does the host immune syst...
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Trypanosoma cruzi (T. cruzi) is an intracellular protozoan parasite and the etiological agent of Chagas disease, a chronic infectious illness that affects millions of people worldwide. Although the role of TLR and Nod1 in the control of T. cruzi infection is well-established, the involvement of inflammasomes remains to be elucidated. Herein, we dem...
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NAIP5/NLRC4 (neuronal apoptosis inhibitory protein 5/nucleotide oligomerization domain-like receptor family, caspase activation recruitment domain domain-containing 4) inflammasome activation by cytosolic flagellin results in caspase-1-mediated processing and secretion of IL-1β/IL-18 and pyroptosis, an inflammatory cell death pathway. Here, we foun...
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Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study we show that the Nlrp3 inflamm...
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Pathogens are detected by innate immune receptors that, upon activation, orchestrate an appropriate immune response. Recent studies revealed the intracellular signaling cascades involved in the TLR-initiated immune response to Brucella abortus infection. However, no report has elucidated the role of inflammasome receptors in Brucella recognition. T...
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Recently our group described that Nattectin, a C-type lectin of the venom of Thalassophryne nattereri shows a potent pro-inflammatory capacity. Here, we demonstrated that Nattectin is able to induce M1 macrophage marker iNOS, and up-regulate the expression of MHC class II, CD80, CD86 and CD40 molecules. The increase in MHC class II and CD49a integr...
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Epitope-specific CD8+ T cell-mediated immune responses of infected and/or immunized immunized C57BL/6 mice. A) C57BL/6 mice were immunized i.m. with 2×108 pfu/mouse of the indicated recombinant adenovirus. Seven days later, half of the mice were challenged s.c. with 104 trypomastigotes of the Y strain of T. cruzi. B) Twenty seven days after immuniz...
Data
Phenotypic characterization of epitope-specific CD8+ T cells induced by infection of genetically deficient C57BL/6 mice with Y strain of T. cruzi. C57BL/6 mice (WT, MyD88, IL-12/IL-23 KO or IFN-1 receptor KO) were infected s.c. with 104 blood forms of T. cruzi Y strain. Control mice were naive mice of the different strains. Fourteen days after infe...
Data
Phenotypic characterization of specific CD8+ T cells of infected and/or AdASP-2 immunized C57BL/6 mice. A) Mice were immunized i.m. with 2×108 pfu of the indicated recombinant adenovirus and challenged s.c. with 104 trypomastigotes of T. cruzi. B) Control cells were CD8+ T cells from naive mice (red lines). Splenic cells were stained with anti-CD8,...
Data
Phenotypic characterization of specific CD8+ T cells induced by T. cruzi infection or AdASP-2 immunization. C57BL/6 mice were infected or immunized as described in the legend of Figure 2. Control mice were naive mice. A) Twenty-eight or 14 days after infection or immunization, respectively, these mice had their splenic cells stained with anti-CD8,...
Data
Parasitemia and kinetics of specific CD8+ T cell-mediated immune responses during infection or vaccination. A) Parasitemia of C57BL/6 mice infected s.c. with 104 bloodstream trypomastigotes of T. cruzi B) Mice were infected s.c. or not with T. cruzi trypomastigotes as described above. In parallel, mice were immunized i.m. with AdASP-2 vaccine (2×10...
Data
Specific CD8+ T cell-mediated immune responses of infected, immunized or infected AdASP-2 immunized C57BL/6 mice. A) C57BL/6 mice were immunized i.m. with 2×108 pfu/mouse of the indicated recombinant adenovirus. Seven days later, half of the mice were challenged s.c. with 104 trypomastigotes of the Y strain of T. cruzi. B) Twenty one, days after im...
Data
Phenotypic characterization of specific CD8+ T cells of infected and/or AdTS immunized BALB/c mice. A) Thirty five days after adenovirus immunization, we estimated the frequencies of H2Kd- IYNVGQVSI+ CD8+ cells. Because some of these mice were challenged 7 days after immunization, this date represents 28 days after challenge with parasites (Gr. 2 a...
Data
Specific CD8+ T cell-mediated immune responses of infected and/or AdTS immunized BALB/c mice. A) BALB/c mice were immunized i.m. with of Adβ-gal or AdTS vaccine (2×108 pfu/mouse). One week later, half of the mice were challenged s.c. with trypomastigotes of the Brazil strain of T. cruzi (103 bloodstream parasites/mouse). B) Parasitemia (per mL) was...
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MHC class Ia-restricted CD8(+) T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8(+) T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, cau...
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Plasmodium chabaudi infection induces a rapid and intense splenic CD4(+) T cell response that contributes to both disease pathogenesis and the control of acute parasitemia. The subsequent development of clinical immunity to disease occurs concomitantly with the persistence of low levels of chronic parasitemia. The suppressive activity of regulatory...
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Foxp3(+)CD25(+)CD4(+) regulatory T cells are vital for peripheral tolerance and control of tissue inflammation. In this study, we characterized the phenotype and monitored the migration and activity of regulatory T cells present in the airways of allergic or tolerant mice after allergen challenge. To induce lung allergic inflammation, mice were sen...
Data
SSC profile discriminates granulocytes and peritoneal MØ subsets. (A) Granulocytes present a particular SSC profile (Gray dots, total PC; Black dots, indicated F4/80+ population), which were used for their exclusion in sequential analysis. (B) Plots show the sequential gates used for the exclusion of granulocytes and the subsequent identification o...
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The peritoneal cavity (PerC) is a singular compartment where many cell populations reside and interact. Despite the widely adopted experimental approach of intraperitoneal (i.p.) inoculation, little is known about the behavior of the different cell populations within the PerC. To evaluate the dynamics of peritoneal macrophage (MØ) subsets, namely s...
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Innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic Nlrc4 (NOD-like receptor family CARD (caspase activation recruitment domain) domain containing 4)/Naip5 (neuronal apoptosis inhibitory protein 5). TLR5 activates inflammatory genes through MYD88 pathway, whereas Nlrc4 and Naip5 assemble multiprotein complexes calle...
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Cell death and differentiation is a monthly research journal focused on the exciting field of programmed cell death and apoptosis. It provides a single accessible source of information for both scientists and clinicians, keeping them up-to-date with advances in the field. It encompasses programmed cell death, cell death induced by toxic agents, dif...
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Cells can die by distinct mechanisms with particular impacts on the immune response. In addition to apoptosis and necrosis, recent studies lead to characterization of a new proinflammatory form of cell death, pyroptosis. TLR and NLR, central innate immune sensors, can control infections by modulating host cell survival. In addition, TLRs can promot...
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The peritoneal cavity (PerC) is a unique compartment within which a variety of immune cells reside, and from which macrophages (MØ) are commonly drawn for functional studies. Here we define two MØ subsets that coexist in PerC in adult mice. One, provisionally called the large peritoneal MØ (LPM), contains approximately 90% of the PerC MØ in unstimu...
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The physiopathology of Chagas' disease has been largely defined in murine infections with virulent strains which partially represent parasite diversity. This report reviews our studies with Sylvio X10/4 parasites, a Trypanosoma cruzi clone that induces no acute phase but in C3H/He mice leads to chronic myocarditis resembling the human disease.
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Antigen-presenting cells (APCs) control T-cell responses by multiple mechanisms, including the expression of co-stimulatory molecules and the production of cytokines and other mediators that control T-cell proliferation, survival and differentiation. Here, we demonstrate that soluble factor(s) produced by Toll-like receptor (TLR)-activated APCs sup...
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Background: Epidemiological and experimental data suggest that bacterial lipopolysaccharides (LPS) can either protect from or exacerbate allergic asthma. Lipopolysaccharides trigger immune responses through toll-like receptor 4 (TLR4) that in turn activates two major signalling pathways via either MyD88 or TRIF adaptor proteins. The LPS is a pro-T...
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Synthetic oligonucleotides (ODNs) containing immunostimulatory CpG motifs (CpG) are a new class of adjuvants suitable for the development of recombinant vaccines. Here we describe that endogenous interferon (IFN) was critical for the adjuvant activity of CpG ODN as genetically deficient mice developed significantly lower IgG antibody titers followi...
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Highly virulent strains of Trypanosoma cruzi are frequently used as murine models of Chagas' disease. However, these strains do not fully represent the spectrum of parasites involved in the human infection. In this paper, we analysed parasitaemia, mortality, tissue pathology and parasite-specific IgG serum levels in immune-deficient mice infected w...
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Besides the established role of interleukin-12 (IL-12) and IL-18 on interferon-gamma (IFN-gamma) production by natural killer (NK), T, and B cells, the effects of these cytokines on macrophages are largely unknown. Here, we investigated the role of IL-12/IL-18 on nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production by CD11b(+) a...
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In the present work, we show that intracellular Trypanosoma cruzi is rarely found in the livers of acutely infected mice, but inflammation is commonly observed. The presence of numerous intrahepatic amastigotes in infected gamma interferon (IFN-γ)-deficient mice corroborates the notion that the liver is protected by an efficient local immunity. The...
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We have previously shown that macrophages from interleukin (IL)-12p40 gene knockout (IL-12/IL-23-/-) mice have a bias towards the M2 activation profile, spontaneously secreting large quantities of transforming growth factor-beta1 (TGF-beta1) and producing low levels of nitric oxide (NO) in response to lipopolysaccharide (LPS) and interferon-gamma (...
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The role of B7/CD28 costimulatory pathway in the polyclonal and specific lymphocyte activation induced by blood stages of Plasmodium chabaudi AS was investigated in CD28 gene knockout (CD28(-/-)) and C57BL/6 (CD28(+/+)) mice. Analysis of the spleen during the acute infection revealed a similar increase in T and B cell populations in both groups of...
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Challenge of 1-yr Trypanosoma cruzi chronically infected mice with trypomastigotes results in a consistent reduction of parasite dissemination that correlates with spleen activation and increase in the anti-T. cruzi effector immune mechanisms. That is, parasite challenge results not only in elimination of the inoculum but also in a drastic decrease...
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The present review illustrates the current knowledge on the autocrine effect of IL-12, and the putative contribution of IL-23, on macrophages and dendritic cells, focusing on cell activation and microbicidal activity. Here, we present convincing evidence that IL-12 is not only a connective element between accessory cells and lymphocytes, but it is...
Article
The present review illustrates the current knowledge on the autocrine effect of IL-12, and the putative contribution of IL-23, on macrophages and dendritic cells, focusing on cell activation and microbicidal activity. Here, we present convincing evidence that IL-12 is not only a connective element between accessory cells and lymphocytes, but it is...
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Chagas’ disease is a chronic infection caused by Trypanosoma cruzi and represents an important public health burden in Latin America. Frequently the disease evolves undetectable for decades, while in a significant fraction of the affected individuals it culminates in death by heart failure. Here, we describe a novel murine model of the chronic infe...
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Aiming to clarify the role of endogenous interleukin-12 (IL-12) in protective immunity against blood stages of Plasmodium chabaudi chabaudi (AS), we evaluated the course of infection in IL-12p40 gene knockout (IL-12p40KO) and wild-type (WT) C57BL/6 mice, focusing (1) on the ability of T cells to develop adequate type 1 responses and (2) on the pote...
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Recent studies have provided evidence that macrophages from Th1-prone mouse strains respond with an M1 profile, and macrophages from Th2-prone mouse strains respond with an M2 profile, characterized by the dominant production of NO or TGF-beta 1, respectively. We have shown that peritoneal macrophages from IL-12p40 gene knockout mice have a bias to...
Article
The mechanisms by which antibodies interfere with Plasmodium growth are still under debate. Characterizing the asexual erythrocyte stages susceptible to antibodies from hyperimmune individuals is therefore a relevant contribution to vaccine research. In this study, using a virulent and synchronous murine malaria parasite, Plasmodium chabaudi chabau...

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