Elaine Raniero Fernandes

Immunopathogenesis of dengue hemorrhagic fever: Contribution to the study of human liver lesions

Dengue infection is an important tropical disease worldwide. The host immune response has been studied in order to better understand lesion mechanisms. It was performed an immunohistochemical study in 14 specimens of liver from patients with dengue hemorrhagic fever (DHF) to characterize cytokines and some factors present in liver lesions and their possible role in the pathogenesis of hepatic injury. Portal tract and hepatic acinus presented high expression of TLR2, TLR3, IL6, and granzyme B. Hepatic acinus also presented iNOS, IL18, and TGF‐beta. Cells expressing IL12, IL13, JAk1, STAT1, and NF‐κB were rarely visualized. Treg cells foxp3+ were absent. TLR2 and TLR3 seem to participate in cellular activation and cytokine production. Cytotoxic response seems to play a role. Although TGF‐beta promotes the activation of Foxp3+ regulatory T cells, IL6 can significantly suppresses their generation. The expression of Treg cells is diminished probably as a result of the high frequency of these cytokines. Both cytokines play a role in the increased vascular permeability and edema observed in dengue liver specimens, with consequent plasma leakage and severity of the disease. It was observed a regular expression of IL‐18 in hepatocytes and lymphocytes of the inflammatory infiltrate in portal tract, which reflects the acute inflammatory response that occurs in the liver and contributes to hepatic injury. At least in part, the increased number of cells expressing IL‐18 could play a role of “up” regulation of FasL and correlate to the phenomenon of apoptosis, a mechanism of destruction of hepatocytes in DHF. J. Med. Virol. 86:1193–1197, 2014.

Immunohistochemistry and polymerase chain reaction on paraffin-embedded material improve the diagnosis of cutaneous leishmaniasis in the Amazon region

Background  Recently, there has been an increase in the incidence of cutaneous leishmaniasis (CL), which represents an important health problem. This increase may be related to the epidemiologic expansion of the infective agent and the increase in tourism in tropical areas. The difficulty in clinical diagnosis, mainly in areas in which CL is not the first consideration of local physicians, has intensified efforts to describe diagnostic tests, which should be specific, sensitive, and practical. Amongst the new tests described are those including nucleic acid amplification (polymerase chain reaction, PCR) and immunohistochemistry (IHC).

In situ apoptosis of adaptive immune cells and the cellular escape of rabies virus in CNS from patients with human rabies transmitted by Desmodus rotundus

The aim of the current study was to investigate the apoptosis of neurons, astrocytes and immune cells from human patients that were infected with rabies virus by vampire bats bite. Apoptotic neurons were identified by their morphology and immune cells were identified using double immunostaining. There were very few apoptotic neurons present in infected tissue samples, but there was an increase of apoptotic infiltrating CD4+ and TCD8+ adaptive immune cells in the rabies infected tissue. No apoptosis was present in NK, macrophage and astrocytes. The dissemination of the human rabies virus within an infected host may be mediated by viral escape of the virus from an infected cell and may involve an anti-apoptotic mechanism, which does not kill the neuron or pro-apoptosis of TCD4+ and TCD8+ lymphocytes and which allows for increased proliferation of the virus within the CNS by attenuation of the adaptive immune response.

The effects of human herpesvirus 8 infection and interferon‐γ response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus‐infected and uninfected individuals

Background  Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV‐8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary.

Revisiting Langerhans cells in paracoccidioidomycosis: expression of CD207/langerin in human cutaneous and mucosal lesions.

Langerhans cells are identified by the expression of langerin. We detected this molecule in cutaneous and mucosal lesions in paracoccidioidomycosis, an important infection in Latin America. Langerin+ cells were scarcely distributed, with short dendrites in epidermis and epithelium and were frequent in the dermis and corium, in the inflammatory infiltrate and granulomas. Mucosal lesions presented a higher expression of langerin in lesions with loose granulomas. For the first time we presented the expression of langerin in paracoccidioidomycosis. Positive cells in dermis and corium could represent migrating Langerhans cells or a new subset of langerin+ cells with a role in paracoccidioidomycosis.

Chronic colitis associated with HIV infection can be related to intraepithelial infiltration of the colon by CD8+ T lymphocytes

Gastrointestinal complications in AIDS patients with diarrhoea are common clinical manifestations, frequently diagnosed by colonoscopy as non-specific colitis. We retrospectively study colon biopsies diagnosed as chronic colitis associated with HIV (CCH). Biopsies were sorted as patients with AIDS (serum CD4 <200 cell/mm3) but without any clear infectious process (n = 12) and patients without HIV infection (n = 24). There are low numbers of CD4+ T lymphocytes in lamina propria of AIDS patients, but CD8+ T populations in this area appear to be similar in all studied groups, regardless of HIV infection or laboratory evidence of a specific agent. We found the clear evidence of CD8+ T cells infiltration in colonic mucosa in HIV patients with microscopic colitis. An imbalance of lymphocyte subpopulations in the colon, both in the lamina propria and epithelium, could result in an intraepithelial CD8 infiltration, involved in the pathogenesis of CCH in AIDS patients.

Immunological aspects of rabies: a literature review

Rabies is a lethal disease caused by the neurotropic virus rabies virus (RABV), and it remains an important public health problem globally. It is known that the host immune response is important for control of viral infection and promoting viral clearance. In this context, it is well documented that, in addition to RABV neutralizing antibody, interferons and cell-mediated immunity also have an important role in preventing the establishment of disease. On the other hand, RABV suppresses host immunity through different mechanisms, for example, direct inhibition of host gene expression, sequestration of pathogen-associated molecular patterns, or modification of cytokine signalling pathways, which hinder the protective host immune responses to RABV infection. Here, we review the immunological aspects of rabies, highlighting innate and adaptive immunity, as well as the host evasion immune mechanisms used by the virus. Finally, we briefly discuss how this knowledge can direct new research and be harnessed for future therapeutic strategies.

Immunohistochemical study of the cellular immune response in human Pneumocystis carinii pneumonia

OBJETIVO: Trabalhos experimentais demonstram que as defesas do hospedeiro frente ao Pneumocystis carinii incluem interacoes complexas entre as celulas imunes, principalmente linfocitos TCD4+ e macrofagos alveolares. Sendo esse um agente importante associado as imunodeficiencias, nosso objetivo foi caracterizar a resposta inflamatoria em pulmao de necropsias de pacientes com AIDS. METODOS: Foram selecionadas 25 necropsias com diagnostico de pneumonia por Pneumocystis carinii para pesquisa imuno-histoquimica de linfocitos TCD4+, TCD8+, macrofagos CD68+, celulas NK CD57+ e celulas com expressao de TNF-alfa. As celulas imunomarcadas foram quantificadas e analisadas estatisticamente. RESULTADOS: Todos os especimes evidenciaram elevado parasitismo na luz dos alveolos. Observou-se espessamento septal com infiltrado inflamatorio constituido predominantemente por linfocitos e macrofagos. Houve diminuicao no numero de linfocitos TCD4+ e aumento de linfocitos TCD8+, macrofagos e celulas NK. No septo alveolar frequentemente observaram-se celulas expressando TNF-alfa. CONCLUSOES: A imunossupressao relacionada a AIDS induz a diminuicao de linfocitos TCD4+ e favorece a permanencia de elevado parasitismo. Os componentes celulares que caracterizam o infiltrado inflamatorio contribuem para os danos irreversiveis no pulmao desses pacientes.

Wave expansion of CD34+ progenitor cells in the spleen in rodent malaria.

Defense against malaria depends upon amplification of the spleen structure and function for the clearance of parasitized red blood cells (pRBC). We studied the distribution and amount of CD34(+) cells in the spleens of mice infected with rodent malaria. We sought to identify these cells in the spleen and determine their relationship to infection. C57BL/6J mice were infected with self-resolving, Plasmodium chabaudi CR, or one of the lethal rodent malaria strains, P. chabaudi AJ and P. berghei ANKA. We then recorded parasitemia, mortality, and the presence of CD34(+) cells in spleen, as determined by immunohistochemistry and flow cytometry. In the non-lethal strain, the spleen structure was maintained during amplification, but disrupted in lethal models. The abundance of CD34(+) cells increased in the red pulp on the 4th and 6th days p.i. in all models, and subsided on the 8th day p.i. Faint CD34(+) staining on the 8th day p.i., was probably due to differentiation of committed cell lineages. In this work, increase of spleen CD34(+) cells did not correlate with infection control.

Street rabies virus strains associated with insectivorous bats are less pathogenic than strains isolated from other reservoirs

ABSTRACT Rabies is a fatal and viral zoonosis that causes acute, progressive encephalitis and remains an important concern in public health. In the last few years, there has been a change in the epidemiological profile of rabies after implementing canine rabies control in the Americas, which has led to a significant increase in both human and pet cases of rabies associated with insectivorous bats. Thus, it is important to understand the pathogenesis caused by Rabies virus (RABV) isolates from insectivorous bats. Viral growth kinetics, cell‐to‐cell spread and virus uptake in vitro were analyzed for RABV isolates from Eptesicus furiralis and Myotis nigricans. For pathogenesis evaluation, mice were inoculated with RABV isolates from Eptesicus furiralis and Myotis nigricans, and clinical signs were observed for 40 days. We observed that the insectivorous bat strains showed a higher replication rate, faster cell‐to‐cell spread and delayed virus uptake in N2a cells. Furthermore, after the first sign of a clinical infection, mice infected with Myotis nigricans and Eptesicus furiralis isolates succumbed rapidly (6 ± 9 days) compared with RABV strains associated with other reservoirs. Our results show that the insectivorous bat RABV strains are less pathogenic for mice than strains associated with other reservoirs. In addition, this study also indicates that the differences in the biological characteristics of the RABV strains are important to their pathogenicity. An enhanced understanding of rabies pathogenesis may be important for the development of novel therapies for humans and in the implementation of rabies control strategies. HighlightsInsectivorous RABV strains were less pathogenic to mice than strains associated with other reservoirs.Insectivorous strains showed a higher replication rate, faster cell‐to‐cell spread and delayed virus uptake in NA cells.There is no correlation between pathogenicity and the replication of street viruses.