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Item Brazilian green propolis hydroalcoholic extract as a therapeutic adjuvant to treat cutaneous leishmaniasis.(2020) Cunha, Beatriz Carvalho; Miranda, Marina Barcelos de; Afonso, Luís Carlos Crocco; Abreu, Sheila Rago Lemos; Testasicca, Miriam Conceição de Souza; Silva, Gisele Rodrigues da; Moura, Sandra Aparecida Lima deCutaneous leishmaniasis is caused by Leishmania parasites. There are a limited number of drugs to treat the cutaneous leishmaniasis, and most of them cause severe adverse effects. Therefore, new therapeutic strategies to treat cutaneous leishmaniasis should be developed. In this study, a standardized Brazilian green propolis (BGP) hydroalcoholic extract (Cytopropolis®, Nectar Pharma Brazil) was evaluated as a therapeutic adjuvant, aiming at the treatment of cutaneous leishmaniasis. The antileishmanial effects of different concentrations of BGP hydroalcoholic extract (500, 250, 125, 62.5, 31.25, 15.6, 7.8, and 3.9 µg ml−1) were determined in vitro against amastigotes and promastigotes and in a murine model of leishmaniasis. High concentrations of BGP hydroalcoholic extract (500, 250, 125, and 62.5 µg ml−1) reduced the viability of promastigotes. All concentrations acted against amastigotes. BGP hydroalcoholic extract (500 and 250 µg ml−1) decreased the number of promastigotes in macrophages. In addition, after 2 weeks of oral treatment, BGP hydroalcoholic extract (250 mg/kg/day) decreased the parasites and induced the macrophage infiltration in the lesion caused by the Leishmania amazonensis on the paw of mice. BGP hydroalcoholic extract may represent a therapeutic adjuvant to treat cutaneous leishmaniasis.Item CD8þT cells are not required for vaccine-induced immunity against Leishmania amazonensis in IL-12/23P40_/_ C57BL/6 mice.(2007) Hernández Sanabria, Mayra Xiomara; Afonso, Luís Carlos Crocco; Golgher, Denise; Tafuri, Wagner Luiz; Vieira, Leda QuerciaVaccine-induced protection against leishmaniasis is largely dependent on cell-mediated type 1 response and IL-12-driven IFN-g production. Surprisingly, our previous data showed that IL-12/23p40_/_ mice could be vaccinated against L. amazonensis and were able to produce limited amounts of IFN-g. Since the role of CD8þT in immunization against L. amazonensis is obscure, the aim of this study was to evaluate the effects of CD8þ cells in protection against L. amazonensis in IL-12/23p40_/_ mice. In order to deplete CD8þ cells, one group of vaccinated animals was treated with anti-CD8 mAb. Infection was followed for 8 weeks. The vaccinated CD8þ-depleted group developed smaller lesions than the non-depleted group. CD8 depletion did not affect tissue parasitism or antibody response against the parasite, and treated animals displayed milder inflammation and better tissue integrity. IFN-g production in spleen and draining lymph node was impaired in the depleted group, suggesting that CD8þ cells produced this cytokine in IL-12-independent vaccination. Such results suggest that this T cell subset contributes to augmented pathology in IL12/23p40_/_ mice vaccinated and challenged with L. amazonensis. Although these cells could produce some IFN-g the in the absence of IL-12, they do not affect the parasite tissue load.Item Coinfection with Toxoplasma gondii inhibits antigen-specific Th2 immune responses, tissue inflamation, and parasitism in BALB/c mice infected with Leishmania major.(1999) Santiago, Helton da Costa; Oliveira, Milton Adriano Pelli de; Bambirra, Eduardo Alves; Faria, Ana Maria Caetano de; Afonso, Luís Carlos Crocco; Oliveira, Leda Quercia; Gazzinelli, Ricardo TostesLesion size, cellular infiltration, and tissue parasitism in the footpads of BALB/c mice infected with Leishmania major were all dramatically inhibited during acute but not chronic infection with Toxoplasma gondii. Similarly, acute but not chronic toxoplasmosis at the time of infection with L. major had a strong inhibitory effect on development of acquired immune responses mediated by Th2 lymphocytes. In contrast, no mItem Development of chronic cardiomyopathy in canine Chagas disease correlates with high IFN-g, TNF-a, and low IL-10 production during the acute infection phase.(2009) Guedes, Paulo Marcos da Matta; Veloso, Vanja Maria; Afonso, Luís Carlos Crocco; Caliari, Marcelo Vidigal; Carneiro, Cláudia Martins; Diniz, Lívia de Figueiredo; Silva, Eduardo de Almeida Marques da; Caldas, Ivo Santana; Matta, Maria Adelaide do Valle; Souza, Sheler Martins de; Lana, Marta de; Chiari, Egler; Galvão, Lúcia Maria da Cunha; Bahia, Maria TerezinhaWhen infected with Trypanosoma cruzi, Beagle dogs develop symptoms similar to those of Chagas disease in human beings, and could be an important experimental model for a better understanding of the immunopathogenic mechanisms involved in chronic chagasic infection. This study evaluates IL-10, IFN-g and TNF-a production in the sera, culture supernatant, heart and cervical lymph nodes and their correlation with cardiomegaly, cardiac inflammation and fibrosis in Beagle dogs infected with T. cruzi. Pathological analysis showed severe splenomegaly, lymphadenopathy and myocarditis in all infected dogs during the acute phase of the disease, with cardiomegaly, inflammation and fibrosis observed in 83% of the animals infected by T. cruzi during the chronic phase. The data indicate that infected animals producing IL-10 in the heart during the chronic phase and showing high IL-10 production in the culture supernatant and serum during the acute phase had lower cardiac alterations (myocarditis, fibrosis and cardiomegaly) than those with high IFN-g and TNF-a levels. These animals produced low IL-10 levels in the culture supernatant and serum during the acute phase and did not produce IL-10 in the heart during the chronic phase of the disease. Our findings showed that Beagle dogs are a good model for studying the immunopathogenic mechanism of Chagas disease, since they reproduce the clinical and immunological findings described in chagasic patients. The data suggest that the development of the chronic cardiac form of the disease is related to a strong Th1 response during the acute phase of the disease, while the development of the indeterminate form results from a blend of Th1 and Th2 responses soon after infection, suggesting that the acute phase immune response is important for the genesis of chronic cardiac lesions.Item E-NTPDase (ecto-nucleoside triphosphate diphosphohydrolase) of Leishmania amazonensis inhibits macrophage activation.(2015) Gomes, Rodrigo Saar; Carvalho, Luana Cristina Faria; Vasconcellos, Raphael de Souza; Fietto, Juliana Lopes Rangel; Afonso, Luís Carlos CroccoLeishmania amazonensis, the causal agent of diffuse cutaneous leishmaniasis, is known for its ability to modulate the host immune response. Because a relationship between ectonucleotidase activity and the ability of Leishmania to generate injury in C57BL/6 mice has been demonstrated, in this study we evaluated the involvement of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity of L. amazonensis in the process of infection of J774-macrophages. Our results show that high-activity parasites show increased survival rate in LPS/IFN-gactivated cells, by inhibiting the host-cell NO production. Conversely, inhibition of E-NTPDase activity reduces the parasite survival rates, an effect associated with increased macrophage NO production. E-NTPDase activity generates substrate for the production of extracellular adenosine, which binds to A2B receptors and reduces IL-12 and TNF-a produced by activated macrophages, thus inhibiting NO production. These results indicate that E-NTPDase activity is important for survival of L. amazonensis within macrophages, showing the role of the enzyme in modulating macrophage response and lower NO production, which ultimately favors infection. Our results point to a new mechanism of L. amazonensis infection that may pave the way for the development of new treatments for this neglected disease.Item Early infection with Leishmania major restrains pathogenic response to Leishmania amazonensis and parasite growth.(2008) Lombana, Claudia Zuleida Gonzalez; Santiago, Helton da Costa; Macedo, J. P.; Rego, Virgínia Aparecida Seixas; Russo, Remo de Castro; Tafuri, Wagner Luiz; Afonso, Luís Carlos Crocco; Vieira, Leda QuerciaExperimental models of infection with Leishmania spp. have provided knowledge of several immunological events involved in the resistance mechanism used by the host to restrain parasite growth. It is well accepted that concomitant immunity exists, and there is some evidence that it would play a major role in long-lasting acquired resistance to infection. In this paper, the resistance to Leishmania amazonensis infection in C57BL/6 mice infected with Leishmania major was investigated. C57BL/6 mice, which spontaneously heal lesions caused by infection with L. major, were infected with L. amazonensis at different times before and after L. major. We demonstrated that C57BL/6 mice previously infected with L. major restrain pathogenic responses induced by L. amazonensis infection and decrease parasite burdens by one order of magnitude. Coinfected mice showed production of IFN-_ in lesions similar to mice infected solely with L. major, but higher TNF-_ and nitric oxide synthase (iNOS) mRNA expression was observed. Surprisingly, the restrained pathogenic response was not related to IL-10 production, as evidenced by lower levels of both mRNA, protein expression in lesions from co-infected mice and in co-infections in IL-10−/− mice. Examination of the inflammatory infiltrate at the site of infection showed a reduced number of monocytes and lymphocytes in L. amazonensis lesions. Additionally, differential production of the CCL3/MIP-1_ and CCL5/RANTES was observed. We suggest that the control of lesion progression caused by L. amazonensis in C57BL/6 mice pre-infected with L. major is related to the induction of a down-regulatory environment at the site of infection with L. amazonensis.Item Ecto-nucleotidase activities of promastigotes from leishmania (Viannia) braziliensis relates to parasite infectivity and disease clinical outcome.(2012) Leite, Pauline Martins; Gomes, Rodrigo Saar; Figueiredo, Amanda Braga de; Serafim, Tiago Donatelli; Tafuri, Wagner Luiz; Gomes, Carolina Cavaliéri; Moura, Sandra Aparecida Lima de; Fietto, Juliana Lopes Rangel; Melo, Maria Norma; Dias, Fátima Ribeiro; Oliveira, Milton Adriano Pelli de; Rabello, Ana Lúcia Teles; Afonso, Luís Carlos CroccoBackground: Leishmania (Viannia) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions. Factors leading to this diversity of clinical presentations are not clear, but parasite factors have lately been recognized as important in determining disease progression. Given the fact that the activity of ecto-nucleotidases correlates with parasitism and the development of infection, we evaluated the activity of these enzymes in promastigotes from 23 L. braziliensis isolates as a possible parasite-related factor that could influence the clinical outcome of the disease. Methodology/Principal Findings: Our results show that the isolates differ in their ability to hydrolyze adenine nucleotides. Furthermore, we observed a positive correlation between the time for peak of lesion development in C57BL/6J mice and enzymatic activity and clinical manifestation of the isolate. In addition, we found that L. (V.) braziliensis isolates obtained from mucosal lesions hydrolyze higher amounts of adenine nucleotides than isolates obtained from skin lesions. One isolate with high (PPS6m) and another with low (SSF) ecto-nucleotidase activity were chosen for further studies. Mice inoculated with PPS6m show delayed lesion development and present larger parasite loads than animals inoculated with the SSF isolate. In addition, PPS6m modulates the host immune response by inhibiting dendritic cell activation and NO production by activated J774 macrophages. Finally, we observed that the amastigote forms from PPS6m and SSF isolates present low enzymatic activity that does not interfere with NO production and parasite survival in macrophages. Conclusions/Significance: Our data suggest that ecto-nucleotidases present on the promastigote forms of the parasite may interfere with the establishment of the immune response with consequent impaired ability to control parasite dissemination and this may be an important factor in determining the clinical outcome of leishmaniasis.Item Ectonucleotidases from trypomastigotes from different sources and various genetic backgrounds of Trypanosoma cruzi potentiate their infectivity and host inflammation.(2020) Leite, Ana Luísa Junqueira; Oliveira, Daniela Silva de; Mota, Ludmilla Walter Reis; Carvalho, Luana Cristina Faria; Zimmermann, Fernanda Francine; Paiva, Nívia Carolina Nogueira de; Vieira, Paula Melo de Abreu; Lana, Marta de; Afonso, Luís Carlos Crocco; Silva, André Talvani Pedrosa daDistinct populations of Trypanosoma cruzi interact with mammalian cardiac muscle cells causing different inflammation patterns and low heart functionality. During T. cruzi infection, the extracellular ATP is hydrolyzed to tri- and/or diphosphate nucleotides, based on the infectivity, virulence, and regulation of the inflammatory response. T. cruzi carries out this hydrolysis through the T. cruzi ectonucleotidase, NTPDase-1 (TcNTPDase-1). This study aimed to evaluate the role of TcNTPDase-1 in culture rich in metacyclic trypomastigote forms (MT) and cell culture-derived trypomastigote forms (CT) from Colombiana (discrete typing unit - DTU I), VL-10 (DTU II), and CL (DTU VI) strains of T. cruzi. For this, we measured TcNTPDase-1 activity in suramin-treated and untreated parasites and infected J774 cells and C57BL/6 mice with suramin pre-treated parasites to assess parasitic and inflammatory cardiac profile in the acute phase of infection. Our data indicated a higher TcNTPDase-1 activity for ATP in culture rich in metacyclic trypomastigote forms from Colombiana strain in comparison to those from VL-10 and CL strains. The cell culture-derived trypomastigote forms from CL strain presented higher capacity to hydrolyze ATP than those from Colombiana and VL-10 strains. Suramin inhibited ATP hydrolysis in all studied parasite forms and strains. Suramin pre-treated parasites reduced J774 cell infection and increased nitrite production in vitro. In vivo studies showed a reduction of inflammatory infiltrate in the cardiac tissues of animals infected with cell culture-derived trypomastigote forms from suramin pre-treated Colombiana strain. In conclusion, TcNTPDase-1 activity in trypomastigotes forms drives part of the biological characteristics observed in distinct DTUs and may induce cardiac pathogenesis during T. cruzi infection.Item Germ-free mice produce high levels of interferon-gamma in response to infection with Leishmania major but fail to heal lesions.(2005) Oliveira, Marcia Rosa de; Tafuri, Wagner Luiz; Afonso, Luís Carlos Crocco; Oliveira, Milton Adriano Pelli de; Nicoli, Jacques Robert; Vieira, Etel Rocha; Scott, Phillip; Melo, Maria Norma; Vieira, Leda QuerciaIn order to investigate the importance of the host microbiota on differentiation of T cell subsets in response to infection, Swiss/NIH germ-free mice and conventional (microbiota-bearing) mice were infected with Leishmania major, and lesion development, parasite loads, and cytokine production were assessed. Germ-free mice failed to heal lesions and presented a higher number of parasites at the site of infection than their conventional counterparts. In addition, histopathological analysis indicated a higher density of parasitized macrophages in lesions from germ-free mice than in conventional mice. The initial production of interleukin (IL)-12 and interferon-gamma (IFN-c) in germ-free mice was comparable to the conventional controls. Also, germ-free mice produced elevated levels of IFN-c and lower levels of IL-4 throughout the course of infection, suggesting the development of a Th1 response. Macrophages from germ-free mice exposed to IFN-c and infected with amastigotes in vitro were not as efficient at killing parasites as macrophages from conventional animals. These observations indicate that the microbiota is not essential for the development of Th1 immune responses, but seems to be important for macrophage activation.Item Histopathology of Leishmania major infection : revisiting L. major histopathology in the ear dermis infection model.(2009) Cangussú, Silvia Dantas; Souza, Carolina Carvalho de; Campos, Camila França; Vieira, Leda Quercia; Afonso, Luís Carlos Crocco; Arantes, Rosa Maria EstevesWe describe the relationship between lesion outcome and histopathological hallmarks in susceptible (BALB/c) and resistant (C57BL/6 and IL-4-deficient BALB/c) mouse strains over the course of a 12-week-infection with Leishmania major in the ear. The infiltration of mononuclear cells and polymorphonuclear cells occurred within 6 h and mononuclear cells predominated one week post-infection. Permissive intracellular growth of the pathogen was associated with non-healing lesions. In contrast, tissue damage and clearance of the parasite was observed in healing lesions and was associated with inducible nitric oxide synthase expression. The identification of the struc¬tural components of tissue reaction to the parasite in this study furthers our understanding of subjacent immune effector mechanisms.Item Immune response induced by New World Leishmania species in C57BL/6 mice.(2004) Maioli, Tatiani Uceli; Takane, Erica; Arantes, Rosa Maria Esteves; Fietto, Juliana Lopes Rangel; Afonso, Luís Carlos CroccoIn the present study, C57BL/6 mice were inoculated with metacyclic Leishmania amazonensis or L. braziliensis promastigotes. While these animals were capable of controlling the infection by L. braziliensis, they developed chronic lesions with elevated numbers of parasites when infected by L. amazonensis. The differences in parasite control were associated with a decreased production of IFN-c and TNF by lymph node cells from L. amazonensis-infected mice. Furthermore, these animals presented decreased spleen cell proliferation and activation of germinal centers. In addition, we compared the ability of these parasites to hydrolyze extracellular ATP and AMP. While the ATPase activity of both parasite species was similar, L. amazonensis promastigotes presented higher AMP hydrolytic activity. This increased activity may lead to an increased production of adenosine, which has been shown to present anti-inflammatory activity and may thus be involved in the establishment of the immunosuppression observed in mice infected by L. amazonensis.Item Immune response of bovines stimulated by synthetic vaccine SBm74621 against Rhipicephalus (Boophilus) microplus.(2009) Salcedo, Joaquin Hernan Patarroyo; Viloria, Marlene Isabel Vargas; González, C. Z.; Guzmán, F.; Martins Filho, Olindo Assis; Afonso, Luís Carlos Crocco; Valente, F. L.; Peconick, Ana Paula; Marciano, A. P.; Patarroyo V, A. M.; Sossai, S.Ten-month-old calves Bos taurus taurus were immunized with three doses of SBm74621 with saponin as an adjuvant at 30-day intervals and were evaluated for IgG isotypes, phenotype circulating lymphocytes and changes in the lymph nodes (LN). SBm74621 stimulated the production of predominantly IgG1-isotype IgG antibodies. The lymph nodes exhibited activation at the seventh day after the first immunization, with areas of paracortical and interfollicular hyperplasia and the early formation of germinal centers (GC). Fifteen days after the first immunization, the GC exhibited compartmentalization of cellular populations, a light zone (LZ), a dark zone (DZ) and a mantle. At the same time, hyperplasia of the medullary cords was observed with cells associating with DC cells. Seven days after the first immunization, apoptosis in the DZ and in the paracortical region became evident. By day 15, there was an increase in the medullary cords, which became more numerous at days 35 and 42. PAP-positive cells were found in the paracortical region, medullary cords and GC 7 days after the first immunization. At day 35, there were further strongly PAP-positive cells in the medullary cords. By comparison, none of these changes were observed in the lymph nodes of control groups at any of the days analyzed. The number of CD21+ lymphocytes increased in the immunized groups after the first inoculation, with a maximum number observed at 15 and 10 days after the first and third immunizations, respectively. Compared to pre-immunization counts, the percentage of WC1+ gd T-lymphocytes displayed more variation, increasing 5 days after the second immunization but decreasing over the following days. According to the results, the synthetic anti Rhipicephalus microplus vaccine elicits a complete immune response being T-dependant.Item Immunochemotherapy in american cutaneous leishmaniasis : immunological aspects before and after treatment.(2001) Toledo, Vicente de Paulo Coelho Peixoto de; Mayrink, Wilson; Gollob, Kenneth John; Oliveira, Milton Adriano Pelli de; Costa, Carlos Alberto da; Genaro, Odair; Pinto, J. A.; Afonso, Luís Carlos CroccoIn this study, we evaluated the immune response of patients suffering from cutaneous leishmaniasis treated with two distinct protocols. One group was treated with conventional chemotherapy using pentavalent antimonium salts and the other with immunochemotherapy where a vaccine against cutaneous leishmaniasis was combined with the antimonium salt. Our results show that, although no differences were observed in the necessary time for complete healing of the lesions between the two treatments, peripheral blood mononuclear cells from patients treated by chemotherapy showed smaller lymphoproliferative responses at the end of the treatment than those from patients in the immunochemotherapy group. Furthermore, IFN-production was also different between the two groups. While cells from patients in the chemotherapy group produced more IFN-at the end of treatment, a significant decrease in this cytokine production was associated with healing in the immunochemotherapy group. In addition, IL-10 production was also less intense in this latter group. Finally, an increase in CD8+ -IFN-producing cells was detected in the chemotherapy group. Together these results point to an alternative treatment protocol where healing can be induced with a decreased production of a potentially toxic cytokine.Item Infection with Leishmania major induces interleukin-12 production in vivo.(1994) Vieira, Leda Quercia; Hondowicz, Brian D.; Afonso, Luís Carlos Crocco; Wysocka, Maria; Trinchieri, Giorgio; Scott, PhillipExperimental infections of mice with the protozoan parasite Leishmania major provide an excellent model for defining the conditions required for generation of CD4 ÷ Thl and Th2 cells in vivo. Since interleukin-12 (IL-12) has been implicated in the development of Thl cells, we investigated whether L. major stimulates IL-12 production in vitro or in vivo. Surprisingly, macrophages cultured in vitro failed to produce IL-12 following L. major infection. In contrast, lymph node cells from C3H mice infected for 2 days with L. major produced elevated levels of IL-12. In order to determine if the inability to stimulate IL-12 production was limited to in vitro infections, we infected macrophages in vivo by inoculating L. major into the peritoneal cavity. Peritoneal cells isolated 24 h later exhibited a significant increase in the number of cells producing IL-12. In addition, supernatants harvested from these cells following culture contained elevated levels of IL-12. These data indicate that L. major infection induces increased IL-12 production in mice.Item Influence of normal microbiota on some aspects of the immune response during experimental infection with Trypanosoma cruzi in mice.(2004) Duarte, Rinaldo; Silva, Andréia Marçal da; Vieira, Leda Quercia; Afonso, Luís Carlos Crocco; Nicoli, Jacques RobertTo study the influence of normal associated microbiota on systemic immunological responses during experimental Chagas’ disease, germ-free and conventional NIH Swiss mice were infected with Y strain of Trypanosoma cruzi. Although no statistical differences in mortality and parasitaemia were found, conventional mice showed IFN-ª, TNF-Æ and NO production (P , 0.05) by spleen cell cultures and higher blood levels of immunoglobulins of the IgG2a isotype (P , 0.05) when compared to their germ-free counterparts. Moreover, higher levels of IgG1 were also found in conventional animals. On the other hand, no differences in IL10 production were found between germ-free and conventional mice after infection (P , 0.05). Interestingly, spleen cell cultures from non-infected germ-free mice spontaneously produced higher levels of IL10 than cultures from conventional mice. Moreover, cultures from non-infected germ-free mice responded to T. cruzi antigens with IFN-ª production, contrary to cultures from conventional animals. In conclusion, the presence of the normal microbiota skews the immune response towards production of inflammatory cytokines during experimental infection with T. cruzi in mice. However, the increase in production of cytokines that is linked to resistance to this parasite did not alter the outcome of infection significantly, probably due to high virulence of the Y strain.Item Interferon-γ induced nitric oxide mediates in vitro neuronal damage by Trypanosoma cruzi-infected macrophages.(2007) Leite, Camila Megale Almeida; Galvão, Lúcia Maria da Cunha; Afonso, Luís Carlos Crocco; Cunha, Fernando de Queiroz; Arantes, Rosa Maria EstevesNeuronal lesions and peripheral denervation in Chagas' disease are related to local inflammation; however, the pathogenic mechanisms of neuronal lesions in the heart and megavisceras are still unclear. We investigated the involvement of nitric oxide (NO) on neuronal lesion in co-cultures of neurons and macrophages. Trypanosoma cruzi-infected and interferon-γ (IFN-γ)-activated co-cultures of neurons and wildtype (WT) macrophages showed significant reduction of both neuronal survival and neurite density. These findings correlated with the levels of NO and the expression of inducible nitric oxide synthase (iNOS). Accordingly, neuronal survival rate in the co-cultures was recovered to control levels by treatment of the cultures with the iNOS inhibitor, aminoguanidine. Moreover, neither neuronal survival nor the neurite density was affected in the co-cultures when the macrophages were harvested from iNOS-deficient mice. These results demonstrate that iNOS-derived NO is the major molecule involved in neuronal damage mechanism in our in vitro model of Chagas' disease neuropathology.Item Involvement of the chemokine RANTES (CCL5) in resistance to experimental infection with Leishmania major.(2004) Santiago, Helton da Costa; Oliveira, Carolina Ferreira; Santiago, Luciana; Ferraz, Fernanda Oliveira; Souza, Daniele da Glória de; Freitas, Luiz Antônio Rodrigues de; Afonso, Luís Carlos Crocco; Teixeira, Mauro Martins; Gazzinelli, Ricardo Tostes; Vieira, Leda QuerciaThe expression and putative role of chemokines during infection with Leishmania major in mice were investigated. CCL5 expression correlates with resistance, and blockade of CCL5 rendered mice more susceptible to infection. CCL5 is part of the cascade of events leading to efficient parasite control in L. major infection.Item Lactobacillus delbrueckii UFV-H2b20 increases IFN-γ production and CD39+CD73+ Treg cell numbers in lungs, and protects mice against experimental allergic asthma.(2022) Andrade, Ana Clara Matoso Montuori de; Silva, Ana Elisa Nolasco e; Malacco, Nathalia Luisa Sousa de Oliveira; Vaz, Leonardo Gomes; Afonso, Luís Carlos Crocco; Russo, Remo de Castro; Vieira, Leda Quercia; Santos, Liliane Martins dosAsthma is a disorder characterized by airflow obstruction, inflammation, declining airway function, bronchial hyperresponsiveness and tissue remodelling. Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. The use of probiotics is becoming increasingly studied and recent evidence has suggested that it may provide therapeutic benefits in asthma and other diseases. Lactobacillus delbrueckii UFV-H2b20 fulfils all the requirements to be classified as probiotic. Previous studies have already shown the ability of L. delbrueckii UFV-H2b20 to stimulate the immune system. Our objective was to evaluate the protective effects of L. delbrueckii UFV-H2b20 in experimental allergic asthma. We used a murine model of ovalbumin-induced allergic airway inflammation to mimic allergic asthma. Oral treatment with L. delbrueckii UFV-H2b20 improves respiratory parameters and inhibits the inflammatory response in the lungs by decreasing the numbers of inflammatory monocytes, eosinophils and alveolar macrophages, as well as IgE levels. Treatment increased the IFN-γ/IL-4 cytokine ratio. Levels of IL-10 in the lungs were also increased in treated animals. Our results also showed that the probiotic administration increases the number of CD39+CD73+ T regulatory lymphocytes in the lung, suggesting a role for purinergic signals in the regulation of inflammation promoted by the treatment. Understanding the mechanisms of modulation of the immune system by probiotics could allow the development of probiotic preparations that are safe and have a direct action. Our results suggest that oral administration of L. delbrueckii UFV-H2b20 could be helpful to treat chronic inflammatory airway diseases, such as asthma.Item Lactobacillus delbrueckii UFV-H2b20 induces type 1 cytokine production by mouse cells in vitro and in vivo.(2009) Neumann, Elisabeth; Ramos, M. G.; Santos, Liliane Martins dos; Rodrigues, Ana Cristina Persichini; Vieira, Enio Carlos; Afonso, Luís Carlos Crocco; Nicoli, Jacques Robert; Vieira, Leda QuerciaItem Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A2B adenosine receptor activation.(2012) Figueiredo, Amanda Braga de; Serafim, Tiago Donatelli; Silva, Eduardo de Almeida Marques da; Fernandes, José Roberto Meyer; Afonso, Luís Carlos CroccoDendritic cells (DCs) play an essential role in the modulation of immune responses and several studies have evaluated the interactions between Leishmania parasites and DCs. While extracellular ATP exhibits proinflammatory properties, adenosine is an important anti-inflammatory mediator. Here we investigated the effects of Leishmania infection on DC responses and the participation of purinergic signalling in this process. Bone marrowderived dendritic cells (BMDCs) from C57BL/6J mice infected with Leishmania amazonensis, Leishmania braziliensis or Leishmania major metacyclic promastigotes showed decreased major histocompatibility complex (MHC) class II and CD86 expression and increased ectonucleotidase expression as compared with uninfected cells. In addition, L. amazonensis-infected DCs, which had lower CD40 expression, exhibited a decreased ability to induce T-cell proliferation. The presence of MRS1754, a highly selective A2B adenosine receptor antagonist at the time of infection increased MHC class II, CD86 and CD40 expression in L. amazonensis-infected DCs and restored the ability of the infected DCs to induce T-cell proliferation. Similar results were obtained through the inhibition of extracellular ATP hydrolysis using suramin. In conclusion, we propose that A2B receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response.