Interaction of human complement factor H variants Tyr402 and His402 with Leptospira spp.

Silva, Aldacilene Souza; Valencia, Mónica Marcela Castiblanco; Cianciarullo, Aurora Marques; Vasconcellos, Sílvio Arruda; Barbosa, Angela Silva; Isaac, Lourdes

doi:10.3389/fimmu.2011.00044

Cited by 7 publications

(6 citation statements)

References 41 publications

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“…factor H, C4BP, etc.) [54], [55], [56], [57]. In this study, the central component involved in both the classical and alternative pathways, the complement component 3 (C3) gene [58], was only up-regulated persistently in MPMs during L. interrogans infection ( Figure S5 ).…”

Section: Resultsmentioning

confidence: 69%

Responses of Murine and Human Macrophages to Leptospiral Infection: A Study Using Comparative Array Analysis

Xue

Zhao²,

Yingchao

et al. 2013

PLoS Negl Trop Dis

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Leptospirosis is a re-emerging tropical infectious disease caused by pathogenic Leptospira spp. The different host innate immune responses are partially related to the different severities of leptospirosis. In this study, we employed transcriptomics and cytokine arrays to comparatively calculate the responses of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (HBMs) to leptospiral infection. We uncovered a series of different expression profiles of these two immune cells. The percentages of regulated genes in several biological processes of MPMs, such as antigen processing and presentation, membrane potential regulation, and the innate immune response, etc., were much greater than those of HBMs (>2-fold). In MPMs and HBMs, the caspase-8 and Fas-associated protein with death domain (FADD)-like apoptosis regulator genes were significantly up-regulated, which supported previous results that the caspase-8 and caspase-3 pathways play an important role in macrophage apoptosis during leptospiral infection. In addition, the key component of the complement pathway, C3, was only up-regulated in MPMs. Furthermore, several cytokines, e.g. interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha), were differentially expressed at both mRNA and protein levels in MPMs and HBMs. Some of the differential expressions were proved to be pathogenic Leptospira-specific regulations at mRNA level or protein level. Though it is still unclear why some animals are resistant and others are susceptible to leptospiral infection, this comparative study based on transcriptomics and cytokine arrays partially uncovered the differences of murine resistance and human susceptibility to leptospirosis. Taken together, these findings will facilitate further molecular studies on the innate immune response to leptospiral infection.

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Section: Resultsmentioning

confidence: 69%

Responses of Murine and Human Macrophages to Leptospiral Infection: A Study Using Comparative Array Analysis

Xue

Zhao²,

Yingchao

et al. 2013

PLoS Negl Trop Dis

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“…Nonpathogenic leptospires are rapidly lysed in vitro after Complement activation while pathogenic species are more resistant due to several evasion mechanisms that confer protection when the Alternative, Lectin, or Classical pathways are activated [10, 16]. Pathogenic Leptospira species can bind to host regulatory proteins, such as Factor H (blocking the alternative pathway), C4b binding protein (avoiding the classical and lectin pathways), and vitronectin (blocking MAC formation) [17–20]. They also secrete proteases that cleave Complement proteins and consequently inhibit all three activation pathways [21] and the MAC formation [22].…”

Section: Introductionmentioning

confidence: 99%

Cytokine Profile in Early Infection byLeptospira interrogansin A/J Mice

Bavia

Castro

Amano

et al. 2019

Journal of Immunology Research

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Leptospirosis is considered a neglected disease with an estimated more than one million cases every year. Since rodents are at the same time the main reservoir and generally asymptomatic to Leptospira infection, understanding why some animal species are resistant and others are susceptible to this infection would shed some light in how to control this important zoonosis. The innate immune response against Leptospira is mainly dependent on phagocytosis and activation of the Complement System. In this context, cytokines may drive the early control of infection and the adaptive response. Since the Complement System is important to eliminate leptospires in vivo, we investigated if Complement C5 in A/J mice would modulate the cytokine production during infection by Leptospira interrogans serovar Kennewicki type Pomona Fromm (LPF). Thus, our aim was to investigate the systemic levels of pro- and anti-inflammatory cytokines during Leptospira infection in the blood, liver, lung, and kidney on the third and sixth days of infection in A/J C5+/+ and A/J C5−/− mice. Blood levels of TNF-α, IL-6, IFN-γ, and MCP-1 reached a peak on the third day. Although both mouse strains developed splenomegaly, similar histopathological alterations in the liver and the lung, levels of pro- and anti-inflammatory cytokines were different. A/J C5+/+ mice had higher levels of liver IL-10, IL-1β, IL-12p40, and IL-12p70 and kidney IL-1β, IL-12p40, and IL-12p70 on the sixth day of infection when compared to A/J C5−/− mice. Our results showed that in A/J genetic background, the Complement component C5 modulates a cytokine profile in the liver and kidney of infected mice, which may play a role in the control of disease progression.

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“…Complemento, variando desde a ligação a proteínas reguladoras, como C4BP e FH (Barbosa et al, 2009;Castiblanco-Valencia et al, 2012;Meri et al, 2005;Silva et al, 2011), até a degradação de moléculas de C3 e seus fragmentos por enzimas secretadas no microambiente próximo às leptospiras (Fraga et al, 2014). Esses mecanismos de evasão podem explicar a maior capacidade de leptospiras patogênicas, como a LPF, em sobreviver no soro, enquanto espécies saprófitas, como a L. biflexa, são bastante sensíveis, sendo eliminadas após poucas horas de incubação (Barbosa et al, 2009;Meri et al, 2005) Ao contrário do que inicialmente esperávamos, a infecção das linhagens B6 C5 + e A/J C5 -com doses crescentes de LPF não acarretou em alterações significativas do número de leucócitos circulantes e nas concentrações de ALT e AST no soro e de citocinas pró e antiinflamatórias no fígado dos camundongos infectados.…”

Section: Discussionunclassified

“…Estudos iniciais mostraram a capacidade de diferentes sorovares de leptospiras se ligarem aos reguladores FH e C4BP (Barbosa et al, 2009;Castiblanco-Valencia et al, 2012;Meri et al, 2005;Silva et al, 2011). Em todas as análises foi adotado nível de significância de pelo menos 5%.…”

Section: Importância Do Sistema Complemento Na Leptospiroseunclassified

Importância do componente C5 do sistema complemento para o controle de leptospirose in vivo em modelos murinos.

Castro¹

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AGRADECIMENTOSAos meus pais e minhas irmãs, por tudo o que representam para mim, pelo apoio em todos os momentos, e sem os quais eu não seria o que sou nem estaria onde estou agora.A Prof. Dr. Lourdes, que me aceitou no laboratório e confiou a mim a execução deste projeto, permitindo que eu crescesse profissionalmente e aprendesse não apenas a "executar tarefas", mas a refletir sobre o que está sendo realizado.A Dr. Angela Barbosa, pela ajuda oferecida durante o projeto.Aos professores do Departamento de Imunologia, pelas aulas, discussões e toda a ajuda fornecida nesses últimos três anos.A todos os funcionários do departamento e do instituto, pelo fornecimento e manutenção dos camundongos utilizados neste projeto, o auxílio fornecido desde a inscrição para a prova de ingresso no programa até a entrega desse texto aos professores que compõem a banca, e pela manutenção de um espaço agradável onde pude passar bons momentos.A Fapesp pelo auxílio financeiro fornecido durante toda a execução do projeto.Ao CNPq pelo auxílio financeiro fornecido no início do mestrado.A BioClin pelo fornecimento dos kits para dosagem de parâmetros bioquímicos no soro dos camundongos.A Lorena Bavia, companheira de bons e maus momentos que me recebeu no laboratório e foi muito importante para a minha formação.A todos os colegas e ex-colegas do laboratório (José Antônio, André, Leandro, Alfredo, Marlene, Tatiana, Adriana, Mónica, Karina, Daniella, Lorena), pela ajuda, as risadas e os bons momentos que passamos no laboratório.

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Interaction of human complement factor H variants Tyr402 and His402 with Leptospira spp.

Cited by 7 publications

References 41 publications

Responses of Murine and Human Macrophages to Leptospiral Infection: A Study Using Comparative Array Analysis

Responses of Murine and Human Macrophages to Leptospiral Infection: A Study Using Comparative Array Analysis

Cytokine Profile in Early Infection byLeptospira interrogansin A/J Mice

Importância do componente C5 do sistema complemento para o controle de leptospirose in vivo em modelos murinos.

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