Human kidney damage in fatal dengue hemorrhagic fever results of glomeruli injury mainly induced by IL17

Pagliari, Carla; Quaresma, Juarez Antônio Simões; Kanashiro-Galo, Luciane; Carvalho, Leda Viegas de; Vitoria, Webster Oliveira; Silva, Wellington Luiz Ferreira da; Penny, Ricardo; Vasconcelos, Barbara Cristina Baldez; Vasconcelos, Pedro Fernando da Costa; Duarte, Maria Irma Seixas

doi:10.1016/j.jcv.2015.12.005

Cited by 36 publications

(35 citation statements)

References 27 publications

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“…Parenchyma and circulatory damages found in kidney samples would likely be immune-mediated due to the presence of mononuclear infiltrates in cortical and medullar regions. A recent report correlated kidney injuries of severe dengue cases with the local recruitment of T cells [52]. In line with our findings, authors also found that infiltrated CD8 + T lymphocytes were outnumbered by CD4 + T cells, suggesting an important role of this subpopulation in tissue damages.…”

Section: Discussionsupporting

confidence: 91%

Peripheral Organs of Dengue Fatal Cases Present Strong Pro-Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES-Producing Cells

et al. 2016

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Dengue disease is an acute viral illness caused by dengue virus (DENV) that can progress to hemorrhagic stages leading to about 20000 deaths every year worldwide. Despite many clinical investigations regarding dengue, the immunopathogenic process by which infected patients evolve to the severe forms is not fully understood. Apart from differences in virulence and the antibody cross reactivity that can potentially augment virus replication, imbalanced cellular immunity is also seen as a major concern in the establishment of severe dengue. In this context, the investigation of cellular immunity and its products in dengue fatal cases may provide valuable data to help revealing dengue immunopathogenesis. Here, based in four dengue fatal cases infected by the serotype 3 in Brazil, different peripheral organs (livers, lungs and kidneys) were studied to evaluate the presence of cell infiltrates and the patterns of local cytokine response. The overall scenario of the studied cases revealed a considerable systemic involvement of infection with mononuclear cells targeted to all of the evaluated organs, as measured by immunohistochemistry (IHC). Quantification of cytokine-expressing cells in peripheral tissues was also performed to characterize the ongoing inflammatory process by the severe stage of the disease. Increased levels of IFN-γ- and TNF-α-expressing cells in liver, lung and kidney samples of post-mortem subjects evidenced a strong pro-inflammatory induction in these tissues. The presence of increased RANTES-producing cell numbers in all analyzed organs suggested a possible link between the clinical status and altered vascular permeability. Co-staining of DENV RNA and IFN-γ or TNF-α using in situ hibridization and IHC confirmed the virus-specific trigger of the pro-inflammatory response. Taken together, this work provided additional evidences that corroborated with the traditional theories regarding the “cytokine storm” and the occurrence of uneven cellular immunity in response to DENV as major reasons for progress to severe disease.

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Section: Discussionsupporting

confidence: 91%

Peripheral Organs of Dengue Fatal Cases Present Strong Pro-Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES-Producing Cells

et al. 2016

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“…DENV can infect several cell types in different tissues and organs. Studies in autopsies and biopsies of patients have demonstrated viral presence in monocytes and macrophages in the liver, lung, spleen, brain, kidney, bone marrow, and heart [20][21][22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile

et al. 2019

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Dengue virus (DENV) infections may result in asymptomatic cases or evolve into a severe disease, which involves multiple organ failure. Renal involvement in dengue can be potentially related to an increased mortality. Aiming to better understand the role of DENV in renal injury observed in human fatal cases, post-mortem investigations were performed in four DENV-4 renal autopsies during dengue epidemics in Brazil. Tissues were submitted to histopathology, immunohistochemistry, viral quantification, and characterization of cytokines and inflammatory mediators. Probably due the high viral load, several lesions were observed in the renal tissue, such as diffuse mononuclear infiltration around the glomerulus in the cortical region and in the medullary vessels, hyalinosis arteriolar, lymphocytic infiltrate, increased capsular fibrosis, proximal convoluted tubule (PCT) damage, edema, PCT debris formation, and thickening of the basal vessel membrane. These changes were associated with DENV-4 infection, as confirmed by the presence of DENV-specific NS3 protein, indicative of viral replication. The exacerbated presence of mononuclear cells at several renal tissue sites culminated in the secretion of proinflammatory cytokines and chemokines. Moreover, it can be suggested that the renal tissue injury observed here may have been due to the combination of both high viral load and exacerbated host immune response.

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“…Tissue samples were processed for histopathology using paraffin block inclusion and the hematoxylin and eosin (H&E) method [8–10] and an adapted immunohistochemical Streptavidin Alkaline Phosphatase (SAAP) assay [12–14] and stained using an anti-ZIKV polyclonal antibody serum.…”

Section: Laboratory Testsmentioning

confidence: 99%

Zika virus epidemic in Brazil. I. Fatal disease in adults: Clinical and laboratorial aspects

Azevedo

Araújo

Filho

et al. 2016

Journal of Clinical Virology

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Background Zika virus (ZIKV) was first detected in Brazil in May 2015 and the country experienced an explosive epidemic. However, recent studies indicate that the introduction of ZIKV occurred in late 2013. Cases of microcephaly and deaths associated with ZIKV infection were identified in Brazil in November, 2015. Objectives To determine the etiology of three fatal adult cases. Study design Here we report three fatal adult cases of ZIKV disease. ZIKV infection in these patients was confirmed by cells culture and/or real-time reverse transcriptase polymerase chain reaction (RT-qPCR) and by antigen detection using immunohistochemical assay. Samples of brain and other selected organs taken at autopsy from three patients were also analyzed by histopathological and immunohistological examination. Results The first patient, a 36-year-old man with lupus and receiving prednisone therapy, developed a fulminant ZIKV infection. At autopsy, RT-qPCR of blood and tissues was positive for ZIKV RNA, and the virus was cultured from an organ homogenate. The second patient, a previously healthy female, 16 years of age, presented classic symptoms of Zika fever, but later developed severe thrombocytopenia, anemia and hemorrhagic manifestations and died. A blood sample taken on the seventh day of her illness was positive RT-PCR for ZIKV RNA and research in the serum was positive for antinuclear factor fine speckled (1/640), suggesting Evans syndrome (hemolytic anemia an autoimmune disorder with immune thrombocytopenic purpura) secondary to ZIKV infection. The third patient was a 20-year-old woman hospitalized with fever, pneumonia and hemorrhages, who died on 13 days after admission. Histopathological changes were observed in all viscera examined. ZIKV antigens were detected by immunohistochemistry in viscera specimens of patients 1 and 3. These three cases demonstrate other potential complications of ZIKV infection, in addition to microcephaly and Guillain-Barre syndrome (GBS), and they suggest that individuals with immune suppression and/or autoimmune disorders may be at higher risk of developing severe disease, if infected with ZIKV.

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Human kidney damage in fatal dengue hemorrhagic fever results of glomeruli injury mainly induced by IL17

Cited by 36 publications

References 27 publications

Peripheral Organs of Dengue Fatal Cases Present Strong Pro-Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES-Producing Cells

Peripheral Organs of Dengue Fatal Cases Present Strong Pro-Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES-Producing Cells

Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile

Zika virus epidemic in Brazil. I. Fatal disease in adults: Clinical and laboratorial aspects

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