A5009756763- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Malaria Research and Control
- Phagocytosis and Immune Regulation
- Toxoplasma gondii Research Studies
- Mosquito-borne diseases and control
- Reproductive System and Pregnancy
- Parasites and Host Interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune responses and vaccinations
- Complement system in diseases
- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- Allergic Rhinitis and Sensitization
- Blood Coagulation and Thrombosis Mechanisms
- Sphingolipid Metabolism and Signaling
- Autoimmune and Inflammatory Disorders Research
- Herpesvirus Infections and Treatments
- Macrophage Migration Inhibitory Factor
- Fatty Acid Research and Health
- Food Allergy and Anaphylaxis Research
- Immune cells in cancer
- Epilepsy research and treatment
- Galectins and Cancer Biology
- Amoebic Infections and Treatments
Fundação Oswaldo Cruz
2017-2025
Ministério da Saúde
2018-2023
Faculdades Oswaldo Cruz
2021
Ministério da Saúde
2019
National Institute of Allergy and Infectious Diseases
2011-2017
National Institutes of Health
2011-2017
Universidade Federal do Rio de Janeiro
2004-2017
Foundation for the National Institutes of Health
2012
Fundação Carlos Chagas
2010
Instituto de Biofísica Carlos Chagas Filho
2010
Abstract Clearance of apoptotic exudate neutrophils (efferocytosis) induces either pro- or anti-inflammatory responses in mouse macrophages depending on host genetic background. In this study, we investigated whether neutrophil efferocytosis a stable macrophage phenotype that could be recalled by late restimulation with LPS. Bone marrow-derived previously stimulated but not expressed regulatory/M2b characterized low IL-12 and high IL-10 production following restimulation, increased...
Macrophages are host cells for the pathogenic parasite Leishmania major. Neutrophils die and ingested by macrophages in tissues. We investigated role of macrophage interactions with inflammatory neutrophils control L. major infection. Coculture dead exudate exacerbated growth infected from susceptible BALB, but killed intracellular resistant B6 mice. Coinjection amplified replication vivo prevented Neutrophil depletion reduced load infection Exacerbated required PGE(2) TGF-beta production...
Neutrophils and dendritic cells (DCs) converge at localized sites of acute inflammation in the skin following pathogen deposition by bites arthropod vectors or needle injection. Prior studies mice have shown that neutrophils are predominant recruited infected during earliest stage Leishmania major infection skin, neutrophil depletion promotes host resistance to sand fly transmitted infection. How massive influx aimed wound repair sterilization might modulate function DCs has not been...
Infection of C57BL/6 mice with most Leishmania major strains results in a healing lesion and clearance parasites from the skin. L. Seidman strain ( Lm Sd), isolated patient chronic lesions, despite eliciting strong Th1 response, nonhealing lesion, poor parasite clearance, complete destruction ear dermis. We show here that comparison to strain, Sd elicited early upregulation IL‐1β mRNA IL‐1β‐producing dermal cells prominent neutrophil recruitment infected Mice deficient Nlrp3,...
Abstract We investigated the role of neutrophil elastase (NE) in interactions between murine inflammatory neutrophils and macrophages infected with parasite Leishmania major. A blocker peptide specific for NE prevented from inducing microbicidal activity macrophages. Inflammatory mutant pallid mice were defective spontaneous release NE, failed to induce wild-type macrophages, reduce loads upon transfer vivo. Conversely, purified activated induced dependent on secretion TNF-α. Induction...
Significance Protozoan parasites of the genus Leishmania are transmitted by sand flies and produce diseases in humans ranging from localized cutaneous lesions to fatal visceral infection. Although these clinical outcomes have clear parasite species associations, genes controlling differences not known. We provide, our knowledge, first experimental demonstration genetic exchange fly vector between different species: a strain major infantum. Eleven full genomic hybrids were generated that...
Inflammatory monocytes can be manipulated by environmental cues to perform multiple functions. To define the role of during primary or secondary infection with an intra-phagosomal pathogen we employed Leishmania major-red fluorescent protein (RFP) parasites and multi-color flow cytometry enumerate infected uninfected inflammatory cells in skin. During infection, had altered maturation were initial mononuclear host cell for parasite replication. In contrast, at a distal site mice healed but...
As key cells, able to host and kill Leishmania parasites, inflammatory monocytes/macrophages are potential vaccine therapeutic targets improve immune responses in Leishmaniasis. Macrophage phenotypes range from M1, which express NO-mediated microbial killing, M2 macrophages that might help infection. Resistance Leishmaniasis depends on species, mouse strain, both innate adaptive immunity. C57BL/6 (B6) mice resistant control infection, whereas parasites thrive BALB/c mice, susceptible develop...
Abstract Neutrophils are involved in the initial steps of most responses to pathogens. In present study, we evaluated effects interaction apoptotic vs. necrotic human neutrophils on macrophage infection by Leishmania amazonensis. Phagocytosis apoptotic, but not viable, Leishmania-infected macrophages led an increase parasite burden via a mechanism dependent TGF-β1 and PGE2. Conversely, infected macrophages’ uptake induced killing L. Leishmanicidal activity was TNF-α neutrophilic elastase....
Chagas' disease is a zoonosis prevalent in Latin America that caused by the protozoan Trypanosoma cruzi. The immunopathogenesis of cardiomyopathy, main clinical problem disease, has been extensively studied but still poorly understood. In this study, we systematically compared clinical, microbiologic, pathologic, immunologic, and molecular parameters two mouse models with opposite susceptibility to acute myocarditis myotropic Colombiana strain T. cruzi: C3H/HeSnJ (100% mortality,...
ABSTRACT The route of pathogen inoculation by needle has been shown to influence the outcome infection. Employing obligately intracellular parasite Leishmania major , which is transmitted in nature following intradermal (i.d.) deposition parasites bite an infected sand fly, we identified differences preexisting and acute cellular responses mice i.d. ear, subcutaneous (s.c.) footpad, or peritoneal cavity (intraperitoneal [i.p.] inoculation). Initiation infection at different sites was...
Numerous experimental Leishmania vaccines have been developed to prevent the visceral and cutaneous forms of Leishmaniasis, which occur after exposure bite an infected sand fly, yet only one is under evaluation in humans. KSAC L110f, recombinant polyproteins delivered a stable emulsion (SE) with TLR4 agonists monophosphoryl lipid A or glucopyranosyl (GLA) shown protection animal models. KSAC+GLA-SE protected against disease following fly transmission major susceptible BALB/c mice. Similar...
ABSTRACT Th1/Th2 cytokines play a key role in immune responses to Leishmania major by controlling macrophage activation for NO production and parasite killing. MDSCs, including myeloid precursors immature monocytes, produce suppress T cell tumor immunity. We hypothesized that NO-producing MDSCs could help immunity L. infection. Gr1hi(Ly6Chi) CD11bhi elicited infection suppressed polyclonal antigen-specific proliferation. Moreover, major-induced killed intracellular parasites NO-dependent...
Abstract Neutrophils are the predominant recruited and infected cells during early stages of Leishmania major infection in skin, depletion neutrophils promotes immunity to transmitted by sand fly bite. In order better understand how acute neutrophilic response suppresses immunity, we assessed consequences interaction between recovered from skin-inoculation site bone marrow-derived dendritic (DCs) vitro . The capture infected, apoptotic DCs completely inhibited their cross-presentation...
We investigated early cellular responses induced by infection with Leishmania major in macrophages from resistant C57/BL6 mice. Infection increased production of reactive oxygen species resident, but not inflammatory peritoneal macrophages. In addition, activation stress-activated protein kinases/c-Jun N-terminal kinases (SAPK/JNK) also expression membrane and soluble FasL, infected remained viable after 48 h. secretion cytokines/chemokines TNF-α, IL-6, TIMP-1, IL-1RA, G-CSF, TREM, KC,...
Ecotin is a potent inhibitor of family S1A serine peptidases, enzymes lacking in the protozoan parasite Leishmania major. Nevertheless, L. major has three ecotin-like genes, termed peptidase (ISP). ISP1 expressed vector-borne procyclic and metacyclic promastigotes, whereas ISP2 also mammalian amastigote stage. Recombinant inhibited neutrophil elastase, trypsin chymotrypsin with K(i)s between 7.7 83 nM. ISP2-ISP3 double null mutants (Deltaisp2/3) were created. These grew normally as but...
Cerebral malaria, the main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both human disease and murine experimental model. In recent years, cognitive deficits related to uncomplicated (non-cerebral) malaria have also been reported chronically exposed residents endemic areas, but not some models non-cerebral malaria. This study aimed at evaluating influence on different behavioural paradigms memory anxiety-like parameters a...
Detrimental effects of malnutrition on immune responses to pathogens have long been recognized and it is considered a main risk factor for various infectious diseases, including visceral leishmaniasis (VL). Thymus target both infection, but its role in the response Leishmania infantum malnourished individuals barely studied. Because we previously observed thymic atrophy significant reduction cellularity chemokine levels mice infected with L. infantum, postulated that microenvironment...
Background The present study investigates implications of a sub-chromosomal deletion in Leishmania infantum strains, the causative agent American Visceral Leishmaniasis (AVL). Primarily found New World leads to absence ecto-3’-nucleotidase/nuclease enzyme, impacting parasite virulence, pathogenicity, and drug susceptibility. factors favoring prevalence widespread geographic distribution these deleted mutant parasites (DEL) NW (NW) are discussed under generated data. Methods We conducted...