KARIN KIRCHGATTER
Projetos de Pesquisa
Unidades Organizacionais
LIM/49 - Laboratório de Protozoologia, Hospital das Clínicas, Faculdade de Medicina - Líder
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- The interaction of two novel putative proteins of Leptospira interrogans with E-cadherin, plasminogen and complement components with potential role in bacterial infection(2019) KOCHI, Leandro T.; V, Luis G. Fernandes; SOUZA, Gisele O.; VASCONCELLOS, Silvio A.; HEINEMANN, Marcos B.; ROMERO, Eliete C.; KIRCHGATTER, Karin; NASCIMENTO, Ana L. T. O.Leptospirosis is a worldwide zoonosis caused by pathogenic species of Leptospira. Leptospires are able to adhere to exposed extracellular matrix in injured tissues and, once in the bloodstream, can survive the attack of the immune system and spread to colonize target organs. In this work, we report that two novel putative proteins, coded by the genes LIC11711 and LIC12587 of L. interrogans serovar Copenhageni are conserved among pathogenic strains, and probably exposed in the bacterial surface. Soluble recombinant proteins were expressed in Escherichia coli, purified and characterized. Both recombinant proteins bound to laminin and E-cadherin, suggesting an initial adhesion function in host epithelial cells. The recombinant protein LIC11711 (rLIC11711) was able to capture plasminogen (PLG) from normal human serum and convert to enzymatically active plasmin (PLA), in the presence of PLG activator. rLIC12587 (recombinant protein LIC12587) displayed a dose dependent and saturable interaction with components C7, C8, and C9 of the complement system, reducing the bactericidal effect of the complement. Binding to C9 may have consequences such as C9 polymerization inhibition, interfering with the membrane attack complex formation. Blocking LIC11711 and LIC12587 on bacterial cells by the respective antiserum reduced leptospiral cell viability when exposed to normal human serum (NHS). Both recombinant proteins could be recognized by serum samples of confirmed leptospirosis, but not of unrelated diseases, suggesting that the native proteins are immunogenic and expressed during leptospirosis. Taken together, our data suggest that these proteins may have a role in leptospiral pathogenesis, participating in immune evasion strategies.
- Recombinant proteins of Plasmodium malariae merozoite surface protein 1 (PmMSP1): Testing immunogenicity in the BALB/c model and potential use as diagnostic tool(2019) ELIZARDEZ, Yelina B.; FOTORAN, Wesley L.; GALISTEO JUNIOR, Andre S. J.; CURADO, Izilda; KESPER JUNIOR, Norival; MONTEIRO, Eliana F.; NETO, Irineu Romero; WUNDERLICH, Gerhard; KIRCHGATTER, KarinBackground Plasmodium malariae is the third most prevalent human malaria-causing species and has a patchy, but ample distribution in the world. Humans can host the parasite for years without presenting significant symptoms, turning its diagnosis and control into a difficult task. Here, we investigated the immunogenicity of recombinant proteins of P. malariae MSP1. Methods Five regions of PmMSP1 were expressed in Escherichia coli as GST-fusion proteins and immunized in BALB/c mice. The specificity, subtyping, and affinity of raised antibodies were evaluated by enzyme-linked immunosorbent assays. Cellular immune responses were analyzed by lymphoproliferation assays and cytokine levels produced by splenocytes were detected by cytometry. Results We found that N-terminal, central regions, and PmMSP1(19) are strongly immunogenic in mice. After three doses, the induced immune responses remained high for 70 days. While antibodies induced after immunization with N-terminal and central regions showed similar affinities to the target antigens, affinities of IgG against PmMSP1(19) were higher. All proteins induced similar antibody subclass patterns (predominantly IgG1, IgG2a, and IgG2b), characterizing a mixed Th1/Th2 response. Further, autologous stimulation of splenocytes from immunized mice led to the secretion of IL2 and IL4, independently of the antigen used. Importantly, IgG from P. malariae-exposed individuals reacted against PmMSP1 recombinant proteins with a high specificity. On the other hand, sera from P. vivax or P. falciparum-infected individuals did not react at all against recombinant PmMSP1 proteins. Conclusion Recombinant PmMSP1 proteins are very useful diagnostic markers of P. malariae in epidemiological studies or in the differential diagnosis of malaria caused by this species. Immunization with recombinant PmMSP1 proteins resulted in a significant humoral immune response, which may turn them potential component candidates for a vaccine against P. malariae.
- Heparin-Binding Protein Release Is Strongly Induced by Leptospira Species and Is a Candidate for an Early Diagnostic Marker of Human Leptospirosis(2019) VIEIRA, Monica L.; PERSSON, Sandra; LOPES-FERREIRA, Monica; ROMERO, Eliete C.; KIRCHGATTER, Karin; NASCIMENTO, Ana Lucia T. O.; HERWALD, HeikoHere we show that heparin-binding protein (HBP) can be used as an early biomarker in patients with leptospirosis. Our experiments further suggest that leptospiral proteins are able to release HBP to an extent that the vascular barrier is impaired.Leptospirosis, caused by spirochetes of the genus Leptospira, is one of the most widespread zoonoses worldwide. Efficient diagnostic methods for early diagnosis of leptospirosis are still lacking, and acute disease presents with nonspecific symptomatology and is often misdiagnosed. The leptospires pathogenic processes and virulence mechanisms remain virtually unknown. In severe infections, hemostatic impairment is frequently observed, and pathophysiological complications often develop when the host response is modulated by the pathogen. The neutrophil heparin-binding protein (HBP) is an inflammatory mediator and potent inducer of vascular leakage. In this study, we found that leptospires and their secreted products induce the release of HBP from stimulated neutrophils through a controlled degranulation mechanism. We acknowledged 2 leptospiral proteins as able to induce HBP degranulation. These findings have clinical implications, as high levels of HBP were detected in serum from patients with leptospirosis, especially at the early phase of the disease. In conclusion, we describe a new mechanism by which the leptospirosis pathophysiological complications may arise, such as vascular leakage and edema formation. We also propose HBP as a new early screening biomarker for human leptospirosis.
- Avian host composition, local speciation and dispersal drive the regional assembly of avian malaria parasites in South American birds(2019) FECCHIO, Alan; BELL, Jeffrey A.; PINHEIRO, Rafael B. P.; CUETO, Victor R.; GOROSITO, Cristian A.; LUTZ, Holly L.; GAIOTTI, Milene G.; PAIVA, Luciana V.; FRANCA, Leonardo F.; TOLEDO-LIMA, Guilherme; TOLENTINO, Mariana; PINHO, Joao B.; TKACH, Vasyl V.; FONTANA, Carla S.; GRANDE, Juan Manuel; SANTILLAN, Miguel A.; CAPARROZ, Renato; ROOS, Andrei L.; BESSA, Rafael; NOGUEIRA, Wagner; MOURA, Thiago; NOLASCO, Erica C.; COMICHE, Kiba J. M.; KIRCHGATTER, Karin; GUIMARAES, Lilian O.; DISPOTO, Janice H.; MARINI, Miguel A.; WECKSTEIN, Jason D.; BATALHA-FILHO, Henrique; COLLINS, Michael D.Identifying the ecological factors that shape parasite distributions remains a central goal in disease ecology. These factors include dispersal capability, environmental filters and geographic distance. Using 520 haemosporidian parasite genetic lineages recovered from 7,534 birds sampled across tropical and temperate South America, we tested (a) the latitudinal diversity gradient hypothesis and (b) the distance-decay relationship (decreasing proportion of shared species between communities with increasing geographic distance) for this host-parasite system. We then inferred the biogeographic processes influencing the diversity and distributions of this cosmopolitan group of parasites across South America. We found support for a latitudinal gradient in diversity for avian haemosporidian parasites, potentially mediated through higher avian host diversity towards the equator. Parasite similarity was correlated with climate similarity, geographic distance and host composition. Local diversification in Amazonian lineages followed by dispersal was the most frequent biogeographic events reconstructed for haemosporidian parasites. Combining macroecological patterns and biogeographic processes, our study reveals that haemosporidian parasites are capable of circumventing geographic barriers and dispersing across biomes, although constrained by environmental filtering. The contemporary diversity and distributions of haemosporidian parasites are mainly driven by historical (speciation) and ecological (dispersal) processes, whereas the parasite community assembly is largely governed by host composition and to a lesser extent by environmental conditions.