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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2019.tde-03082023-161812
Document
Author
Full name
Cinthia Siess Portugal
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Véliz, Mauro Javier Cortez (President)
Carboni, Beatriz Simonsen Stolf
Fonseca, Denise Morais da
Giorgio, Selma
Title in Portuguese
Papel da proteína imunomoduladora CD200 nas infecções de macrófagos por Leishmania (Leishmania) infantum chagasi
Keywords in Portuguese
macrófagos
Leishmania (L.) infantum chagasi
CD200/CD200R
iNOS
oxido nítrico
Abstract in Portuguese
Parasitos do gênero Leishmania desenvolveram estratégias para garantir sua sobrevivência, manipulando mecanismos microbicidas de células de defesa, como macrófagos, e modulando a resposta imunológica do hospedeiro. A glicoproteína CD200, quando induzida no macrófago, inibe o mecanismo leishmanicida mediado por oxido nítrico (NO) na evasão da resposta imune contra L. (L.) amazonensis, espécie associada à leishmaniose cutânea. No entanto, nenhum trabalho descreve o papel de CD200 em infecções de macrófagos pela espécie L. (L.) infantum chagasi, a qual causa leishmaniose visceral, a forma mais grave e letal das leishmanioses. Assim, este trabalho buscou elucidar o papel de CD200, avaliando sua expressão em macrófagos infectados com L. (L.) infantum chagasi ao longo do tempo. Nossos resultados indicam que L. (L.) infantum chagasi induz a expressão de CD200 a partir de 24 até 72 h de infecção, mas o evento não está relacionado com a inibição da resposta do macrófago infectado, visto que a inibição da enzima oxido nítrico sintase induzível (iNOS) pelo inibidor L-NAME, o bloqueio de CD200 com anticorpos ou a adição de CD200Fc solúvel não afetam a proliferação do parasito intracelular. Além disso, mostramos que células do baço apresentam maiores taxas de infecção, o que pode estar relacionado ao acometimento desse órgão por essa espécie de parasito. Experimentos futuros poderão desvendar a funcionalidade da indução de CD200 na infecção por L. (L.) infantum chagasi, a qual pode ser relevante na inibição de outras células que chegam no foco infeccioso ou no processo de migração celular em direção a órgãos afetados durante a leishmaniose visceral.
Title in English
Role of CD200 immunomodulatory protein in macrophage infections by Leishmania (Leishmania) infantum chagasi.
Keywords in English
macrophages
Leishmania (L.) infantum chagas
CD200/CD200R
iNOS
nitric oxide
Abstract in English
Parasites of Leishmania genus evolved different strategies to survive, manipulating microbicidal mechanisms of defense cells such as macrophages, and modulating the immune response of the host. Glycoprotein CD200, when induced in the macrophage, inhibits the leishmanicidal mechanism mediated by nitric oxide (NO) in the immune evasion response by L. (L.) amazonensis, species associated with cutaneous leishmaniasis. However, none report describes the role of CD200 in macrophage infection by L. (L.) infantum chagasi, which causes visceral leishmaniasis, the most lethal and severe form of the disease. Here, we study the role of CD200, analyzing the expression of the ligand in macrophages infected by L. (L.) infantum chagasi in different time points. Our results indicate that L. (L.) infantum chagasi induce CD200 expression from 24 to 72 h of infection, but it was not related to the inhibition of the macrophage response, since inhibition of iNOS by L-NAME, blockage by CD200/CD200R antibodies or addition of CD200Fc did not affect the intracellular parasite proliferation. Furthermore, spleen cells presented higher infection, perhaps due to involvement of this organ in the visceral pathology. Future experiments will allow knowing the primary function of CD200 in L. (L.) infantum chagasi infection, which could be relevant to the inhibitory function in neighbor recruited cells during infection or the cellular migration of Leishmania in infected cells at the different systemic organs during visceral leishmaniasis.
 
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Release Date
2025-08-02
Publishing Date
2023-08-07
 
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