Karina Ramalho Bortoluci's research while affiliated with Universidade Federal de São Paulo and other places

Publications (38)

Article
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The content of tumor-derived extracellular vesicles (EVs) can regulate the tumor microenvironment and functionally acts in favor of cancer aggressiveness. To better elucidate the role of EVs in the interplay between immune system and tumor microenvironment, the purpose of this study was to analyze the effect of head and neck squamous cells carcinom...
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Chagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi . Parasite-specific antibodies, CD8 ⁺ T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl...
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Deficiency in memory formation and increased immunosenescence are pivotal features of Trypanosoma cruzi infection proposed to play a role in parasite persistence and disease development. The vaccination protocol that consists in a prime with plasmid DNA followed by the boost with a deficient recombinant human adenovirus type 5, both carrying the AS...
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Muscle tissue damage is one of the local effects described in bothropic envenomations. Bothropstoxin-I (BthTX-I), from B. jararacussu venom, is a K49-phospholipase A2 that induces a massive muscle tissue injury, and, consequently, local inflammatory reaction. The NLRP3 inflammasome is a sensor that triggers inflammation by activating caspase 1 and...
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This study evaluated the role of endogenous and exogenous annexin A1 (AnxA1) in the activation of the NLRP3 inflammasome in isolated peritoneal neutrophils. C57BL/6 wild-type (WT) and AnxA1 knockout mice (AnxA1-/-) received 0.3% carrageenan intraperitoneally and, after 3 h, the peritoneal exudate was collected. WT and AnxA1-/- neutrophils were then...
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The COVID-19 pandemic is shining a spotlight on the field of immunology like never before. To appreciate the diverse ways in which immunologists have contributed, Nature Reviews Immunology invited the president of the International Union of Immunological Societies and the presidents of 15 other national immunology societies to discuss how they and...
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Chemokine receptor type 3 (CXCR3) plays an important role in CD8⁺ T cells migration during intracellular infections, such as Trypanosoma cruzi. In addition to chemotaxis, CXCR3 receptor has been described as important to the interaction between antigen-presenting cells and effector cells. We hypothesized that CXCR3 is fundamental to T. cruzi-specif...
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Caspase-8 is a master regulator of cell death pathways, although its regulation during inflammation remains elusive. Using elegant mouse genetic approaches, Schwarzer et al. and Tummers et al. revealed the importance of FADD in regulating caspase-8-mediated inflammatory responses and gut homeostasis.
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Efficient induction of effector and long-term protective antigen-specific CD8+ T memory response by vaccination is essential to eliminate malignant and pathogen-infected cells. Intracellular infectious bacteria, including Listeria monocytogenes, have been considered potent vectors to carry multiple therapeutic proteins and generate antigen-specific...
Article
Astrocytes and microglia are the most abundant glial cells. They are responsible for physiological support and homeostasis maintenance in the central nervous system (CNS). The increasing evidences of their involvement in the control of infectious diseases justify the emerging interest in the improvement of methodologies to isolate primary astrocyte...
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Placental malaria (PM) is associated with severe inflammation leading to abortion, preterm delivery, and intrauterine growth restriction. Innate immunity responses play critical roles, but the mechanisms underlying placental immunopathology are still unclear. Here, we investigated the role of inflammasome activation in PM by scrutinizing human plac...
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Antibiotic-induced dysbiosis is a key predisposing factor for Clostridium difficile infections (CDIs), which cause intestinal disease ranging from mild diarrhea to pseudomembranous colitis. Here, we examined the impact of a microbiota-derived metabolite, short-chain fatty acid acetate, on an acute mouse model of CDI. We found that administration of...
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Autophagy and inflammasome activation are cell‐autonomous and cross‐regulated processes involved in host resistance against infections. Our group previously described that NLRP3 inflammasome is required for the control of Trypanosoma cruzi, the causative agent of Chagas disease. However, the involvement of autophagy in this process was unclear. Her...
Article
Trypanossoma cruzi (T. cruzi), the causative protozoan of Chagas disease (CD) invades many cell types, including central nervous system (CNS) cells triggering local lesions and neurological impact. Previous work from our group described NLRP3 inflammasomes as central effectors for the parasite control by macrophages. Recent evidences demonstrate th...
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Glioblastoma (GBM) is an incurable disease ranked among the deadliest solid cancers worldwide. A better understanding on the molecular aspects of this malignancy could contribute to the development of new treatment strategies and help to improve survival rates. Previously, our group had shown that GBM patients expressing the cancer/testis antigen O...
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Pattern Recognition Receptors (PRRs) are proteins capable of recognizing molecules frequently found in pathogens (the so-called Pathogen-Associated Molecular Patterns—PAMPs), or molecules released by damaged cells (the Damage-Associated Molecular Patterns—DAMPs). They emerged phylogenetically prior to the appearance of the adaptive immunity and, th...
Article
Nitric oxide synthase 2, inducible (Nos2) expression is necessary for the microbicidal activity of macrophages. However, NOS2 over-activation causes multiple inflammatory disorders, suggesting a tight gene regulation is necessary. Using cytosolic flagellin as a model for inflammasome-dependent NOS2 activation, we discovered a surprising new role fo...
Data
Suboptimal expansion and cytokine response of OTI CD8+ T cells upon in vivo stimulation with T. cruzi-exposed BMDC-SIINFEKL. OTI cells were adoptively transferred into C57BL/6 mice prior to transfer of control BMDC exposed to LPS only (Gr.1) or BMDC exposed to LPS and loaded with SIINFEKL peptide (Gr. 2) or BMDC previously exposed to T. cruzi and L...
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Suboptimal response of OTI CD8+ T cells upon in vivo stimulation with T. cruzi-exposed BMDC-SIINFEKL in il10-/- deficient mice. a- OTI cells were adoptively transferred into il-10-/- mice prior to transfer of BMDC (Gr.1), BMDC-SIINFEKL (Gr.2) or T. cruzi-exposed BMDC-SIINFEKL (Gr.3). The SIINFEKL-specific immune response was assessed after 5 days....
Data
Cytokine response of OTI and parasite-specific CD8+ T cells upon in vivo stimulation with T. cruzi-exposed BMDC. OTI cells were adoptively transferred into C57BL/6 mice before the transfer of BMDC, BMDC-SIINFEKL (Gr.2), or T. cruzi-exposed BMDC-SIINFEKL (Gr.3). After 5 or 12 days, spleen cells were harvested and restimulated ex vivo with Medium, SI...
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Phenotype of OTI CD8+ T cells upon stimulation with T. cruzi-exposed BMDC-SIINFEKL. OTI cells were adoptively transferred into C57BL/6 mice before the transfer of BMDC (Gr.1), BMDC-SIINFEKL (Gr.2) or T. cruzi-exposed BMDC-SIINFEKL (Gr.3). After 5 days, splenic CD8+ T cells were stained with H-2Kb SIINFEKL tetramers and mAbs to the surface markers a...
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Suboptimal expansion and differentiation of OTI CD8+ T cells upon in vivo stimulation with T. cruzi-exposed splenic DC co-injected with SIINFEKL-loaded splenic DC. a- Experimental design: 1 x 104 OTI cells were adoptively transferred into C57BL/6 mice before the transfer of 5 x 105 DC (Gr.1), 5 x 105 DC-SIINFEKL (Gr.2) or 5 x 105 DC-SIINFEKL and 5...
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Unaltered induction of OTI CD8+ T cell responses upon immunization with AdASP-2-exposed BMDC-SIINFEKL. a- 1 x 104 OTI cells were adoptively transferred into C57BL/6 mice prior to transfer of 5 x 105 control BMDC exposed to LPS only (Gr.1) or 5 x 105 BMDC exposed to LPS and loaded with SIINFEKL peptide (Gr. 2) or 5 x 105 BMDC previously exposed to A...
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BMDC exposed to T. cruzi are able to express cytokine genes and prime CD8+ T cells in vitro. BMDC were left untreated or exposed to T. cruzi for 24 h and/or LPS for 6 h. a- Transcription of the indicated cytokines was assessed by RT-PCR. b- After incubation with SIINFEKL peptide, the ability of these cells to prime naïve OTI CD8+ T cells in vitro w...
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CD4+ T cells induced by T. cruzi-exposed BMDC mediate the suppression of OTI CD8+ T cell priming. a- T. cruzi-exposed BMDC were adoptively transferred into C57BL/6 mice and the splenic CD4+ T cells were sorted after 5 days. These cells (10 x 106/mouse) were adoptively transferred into C57BL/6 mice on the same day of OTI cell transfer and 24 h befor...
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Effect of antibody-mediated CD25+ cell depletion in the in vivo priming of OTI cells by T. cruzi-exposed BMDC. a- OTI cells were adoptively transferred into mice prior to transfer of BMDC (Gr.1), BMDC-SIINFEKL (Gr.2) or T. cruzi-exposed BMDC-SIINFEKL (Gr.3). All animals were treated every 48 h with 0.5 mL of ascite fluid from PC61-injected nude mic...
Data
Primers used in RT-PCR for detecting mRNA levels of cytokines in BMDC. (TIF)
Data
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Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful an...
Article
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...
Article
Full-text available
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...

Citations

... In addition to inflammatory responses mediated by macrophages, the inhibition of inflammasomes is another mechanism used by tumor cells to escape from the immune system (Ghiringhelli et al., 2009). Based on this, the NLRP3 (nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat-containing receptors (NLRs) family pyrin domain containing 3) is one of the best-described inflammasome proteins, and EVs isolated from HNSCC patients, which were enriched in TGF-β signaling molecules, were able to inhibit the induction of pro-IL-1β and pro-caspase-1 proteins, in addition to the downregulation of NLRP3 expression during the priming phase of inflammasome activation (Bottino et al., 2021). Moreover, MG63 osteosarcoma cell-derived EVs induced M2 macrophage differentiation and also enhanced expression of cytokine transcripts, such as IL10, VEGF and TGFB1 in vivo (Cheng et al., 2021). ...
... The assembly of the inflammasome platform is a crucial and wellorganized process that includes many key components, such as upstream sensors that recognize activating signals, adapters, and downstream effectors. Endogenous damage-associated molecular patterns (DAMPs; or host danger signals), which are produced in response to tissue damage, including myonecrosis after snake envenoming, have emerged as another important source of inflammasome activation [2,3]. The nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is triggered by a variety of external stimuli, including venom-isolated toxins, and it can detect additional host-derived signals downstream of these foreign stimuli. ...
... Indeed, FPR1 signaling is important in activating the NLRP3 inflammasome as evidenced by reduced inflammation, leukocyte infiltration, and tissue damage in Fpr-1 KO mice (51), as well as limiting neuroinflammation following stroke (52). Recent work by Galvão et al. demonstrated that AnxA1 co-localizes and directly binds to the NLRP3 (53), thus these anti-inflammatory effects may involve several pathways in addition to FPR signaling including modulation of neutrophils and macrophages (54,55). ANXA1 also facilitates resolution of inflammation by acting on the lipoxin A4 receptor (ALXR) to downregulate polymorphonuclear neutrophil recruitment at the site of inflammation (56). ...
... Given the broad repertoire of these therapies, there are significant variations in risk analyses, with many guidelines and opinions largely agreeing that cell-depletion therapies likely present the highest risk [65,66]. At the same time, the discussion of immunology and immunological terms has become more commonplace as mainstream news sources frequently report on developments in vaccines and antigen and antibody tests; this ''infodemic'' may in turn influence public interest in understanding immunology and immunological health literacy, and interpretations of risk in other contexts [67,68]. Evidence of the effects of COVID-19 on DMT selection and risk monitoring in MS is a rapidly evolving knowledge base, and communications with PwMS should reflect this. ...
... CXCR3 is known to perform important roles in the peripheral immune system. CXCR3 is associated with the recruitment of both CD4 + and CD8 + T cells to the site of infection, IFN-γ secretion from the T cells, and the resultant activation of inflammatory monocytes [26,49]. For example, CXCR3 activation can affect the proliferation and immune responses of macrophages and dendritic cells during infection with Leishmania amazonensis [50,51]. ...
... Post-mortem lung sections has revealed that pulmonary inflammatory responses may induce infiltration of inflammatory cells that trigger strong immune pathogenesis . Mechanisms of inflammatory response and cell death are strongly linked during SARS-CoV-2 infection (Amaral and Bortoluci, 2020). The infection of lung cells activates caspase-8 to trigger cell death pathways, where apoptosis, pyroptosis, and necroptosis are involved. ...
... Proliferative stages of the parasite have been cultured in vitro employing a variety of cell culture lines (e.g., HeLa, Vero, HFF, BeWo) and primary cell cultures (Scheidegger et al., 2005;Müller and Hemphill, 2013), and among them, target cells or tissues (e.g., trophoblast and nervous cells, dendritic cells [DCs] or macrophages) should be highlighted (Guimarães et al., 2008;Dellacasa-Lindberg et al., 2011;Mammari et al., 2014;Witola et al., 2014;Barbosa et al., 2015;da Silva et al., 2017;Pacheco et al., 2020). Most of publications on T. gondii implementing in vitro assays are focused on safety and efficacy assessment of potential antiparasitic drugs (Basto et al., 2017;Murata et al., 2017;Radke et al., 2018) or on demonstrating the role of different host and parasite effectors in the T. gondii lytic cycle (Camejo et al., 2014;Bai et al., 2018;Guo et al., 2019;. ...
... RIP1 kinase is also found to be engaged in apoptosis whereas RIP3 and MLKL solely contributes to necroptosis (11). One of the major foundations of necroptosis is the formation of the necroptotic complex between the RIP1-RIP3-MLKL; phosphorylation of the MLKL protein finally prompts membrane pore formation, cells undergo osmotic pressure changes with its environment and Danger Associated Molecular Pattern (DAMP) are released which further increases inflammation (12)(13)(14). Moreover, initial interaction between Pathogen Associated Molecular Pattern (PAMP like LPS) with Pattern recognition receptor (PRR such as TLRs, NLRs) determine the switch between shared or mutually regulated cell death processes (15,16). ...
... 1 axis activation is associated with MiP outcomes (99), which in principle can be downregulated by autophagy if overactivated ( 5 4 ) . I n a d d i t i o n , a u t o p h a g y c a n b e i n d u c e d b y proinflammatory cytokines such as TNF-a, which induce apoptosis via death receptors and are associated with MiP poor outcomes (14,19,20). ...
... SCFAs are critical regulators of intestine immune function and have immunomodulatory capacities on a variety of immune cells, such as regulatory T cells (Tregs), macrophages, antigen-presenting cells, Type 3 innate lymphoid cells (ILC3), and B cells [59][60][61]. During active immune responses, SCFAs can promote the generation of T helper cells (Th1 and Th17). ...