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1.
Front Immunol ; 12: 716314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804009

RESUMO

Structural changes in the spleen have been reported in several infectious diseases. In visceral leishmaniasis (VL), a severe parasitic disease caused by Leishmania spp., the loss of white pulp accompanies a severe clinical presentation. Hamster model reproduces aspects of human VL progression. In the early stages, a transcriptomic signature of leukocyte recruitment was associated with white pulp hyperplasia. Subsequently, impaired leukocyte chemotaxis with loss of T lymphocytes in the periarteriolar lymphoid sheath occurred. This differential gene expression was subsequently corroborated by transcriptomic profiling of spleens in severe human VL. At the latest stage, spleen disorganization was associated with increasing clinical signs of VL. White pulp disruption was accompanied by decreased DLK1 expression. The expression of CXCL13, CCR5, CCL19, CCR6, CCR7 and LTA decreased, likely regulated by CDKN2A overexpression. Our findings enlighten a pathway implying cell cycle arrest and decreased gene expression involved in spleen organization.


Assuntos
Pontos de Checagem do Ciclo Celular/genética , Quimiotaxia de Leucócito/genética , Leishmaniose Visceral/imunologia , Baço/imunologia , Baço/parasitologia , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Cricetinae , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Hiperplasia/patologia , Leishmaniose Visceral/patologia , Leucócitos/parasitologia , Leucócitos/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Baço/patologia , Transcriptoma
2.
BMC Res Notes ; 13(1): 401, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854763

RESUMO

OBJECTIVE: Acute tubular necrosis (ATN) is a frequent cause of acute kidney injury (AKI). In patients with nephrotic syndrome (NS), AKI demands the differential diagnosis between ATN and rapidly progressive glomerulonephritis. In some cases, conclusive diagnosis is possible only by kidney biopsy. We aimed to study the potential use of urine cytology in the differential diagnosis between ATN and proliferative glomerular lesion in patients with NS. RESULTS: Cell size analysis showed a higher proportion of small cells and a lower proportion of large cells in the urine of patients with AKI. Cells phenotypes were easily defined using cytological preparations. Leukocytes were found to be a primary classifier of NS groups, with higher number in patients with AKI and patients with proliferative glomerular lesions. Although renal biopsy is still required for confirmative diagnosis, our data suggests that urinary cytology can be readily performed and support the differential diagnosis between proliferative glomerular lesion and ATN in patients with NS and AKI.


Assuntos
Injúria Renal Aguda , Necrose Tubular Aguda , Síndrome Nefrótica , Injúria Renal Aguda/diagnóstico , Diagnóstico Diferencial , Humanos , Glomérulos Renais , Necrose Tubular Aguda/diagnóstico , Síndrome Nefrótica/complicações , Síndrome Nefrótica/diagnóstico
3.
Front Immunol ; 11: 653, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32351510

RESUMO

Background: Visceral leishmaniasis (VL) is caused by Leishmania infantum or L. donovani infection. One of the main problems related to this disease is the emergence of severe clinical forms with a lethality of 5-20%, even while under specific treatment. In humans and other species susceptible to fatal VL, such as dogs and hamsters, the disruption of splenic white pulp (WP) is accompanied by disease progression. Control of VL progression is seen in BALB/c mice, as evidenced by a mild clinical presentation and controlled parasite replication in the liver and spleen. In this study, we investigated the features involved in the morphological remodeling of splenic compartments associated with the control of VL progression to death. Methods: We evaluated cohorts of BALB/c mice after 30, 60, and 90 days of infection by L. infantum. Spleen morphology, cell population subsets and cytokine production were studied in the spleen using flow- and histo-cytometry. Results: Intraperitoneal infection with 108 promastigotes of L. infantum led to progressive increases in spleen size at 60 and 90 days after infection. Splenomegaly was the only clinical sign of disease observed. At 30 days after infection, hyperplasia in the WP and decreased numbers of plasmacytoid dendritic cells were observed. The WP hyperplasia subsided at 60 days post-infection. However, the splenomegaly remained in association with increased numbers of macrophages, B and T lymphocytes and plasma cells. An increased number of lymphoid tissue inducer (LTi) cells was observed; these were distributed around the periarteriolar lymphoid sheath in control mice and scattered throughout the red pulp in the Leishmania-infected mice. After 90 days of infection, increased IL-6 and IFN-γ production was seen in the spleen, as well as higher frequencies of follicular and plasmacytoid dendritic cells. Conclusion: The data presented herein emphasizes the potential role of spleen remodeling in the control of severe forms of VL and highlights features potentially involved in this process.


Assuntos
Células Dendríticas/imunologia , Leishmania donovani/fisiologia , Leishmania infantum/fisiologia , Leishmaniose Visceral/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Baço/patologia , Animais , Humanos , Hiperplasia , Interferon gama/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Fenótipo , Baço/parasitologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-30483481

RESUMO

The spleen is a secondary lymphoid organ responsible for immune surveillance against blood-circulating pathogens. Absence of the spleen is associated with increased susceptibility to systemic spread and fatal infection by different pathogens. Severe forms of visceral leishmaniasis are associated with disorganization of spleen compartments where cell interactions essential for splenic immunological function take place. White pulp atrophies, secondary lymphoid follicles and marginal zones vanish, and the boundaries separating white and red pulp blur. Leukocyte populations are reduced or disappear or are replaced by plasma cells. In this paper, we review the published data on spleen disorganization in severe forms of visceral leishmaniasis and propose a histological classification to help the exchange of information among research groups.


Assuntos
Leishmaniose Visceral/patologia , Baço/patologia , Animais , Doença Crônica , Humanos , Leishmania infantum/imunologia , Leishmaniose Visceral/imunologia , Leucócitos , Baço/imunologia
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