Lacaziosis: immunohistochemical evaluation of elements of the humoral response in cutaneous lesions

Lacaziosis is a cutaneous mycosis caused by the fungus Lacazia loboi, described in different countries of Latin America and prevalent in the Amazon region. The ineffective immune response against the agent seems to be related to a Th2 pattern of cytokines. There are few reports exploring elements of the humoral response in these lesions. Our aim was to investigate some elements focusing on B cells, plasma cells and local expression of IgG and IgM antibodies. Forty skin biopsies of lower limbs were selected. The diagnosis of lacaziosis was based on direct mycological examination and histological analysis. The visualization of fungal cells was improved by using Gridley’s staining. An immunohistochemical protocol was performed to detect the expression of B cells, plasma cells, IgG and IgM. A double staining was performed to explore the presence of yeasts in the cytoplasm of keratinocytes, using an anti-AE1 AE3 antibody over Gridley’s staining. The inflammatory infiltrate consisted of macrophages, multinucleated giant cells, lymphocytes, and fibrosis. Fungal cells were frequent in the stratum corneum and in both, the dermis and, in 50% of the specimens, also in the epidermis. Cells expressing IgG were more abundant when compared to cells expressing IgM. B cells and the presence of IgG might indicate that the humoral response promotes a Th2 immune response resulting in an anti-inflammatory phenotype. Our results lead us to suggest a possible role of B cells and immunoglobulins in the mechanisms of lacaziosis pathogenesis

Early and Late Pathogenic Events of Newborn Mice Encephalitis Experimentally Induced by Itacaiunas and Curionópolis Bracorhabdoviruses Infection

In previous reports we proposed a new genus for Rhabdoviridae and described neurotropic preference and gross neuropathology in newborn albino Swiss mice after Curionopolis and Itacaiunas infections. In the present report a time-course study of experimental encephalitis induced by Itacaiunas and Curionopolis virus was conducted both in vivo and in vitro to investigate cellular targets and the sequence of neuroinvasion. We also investigate, after intranasal inoculation, clinical signs, histopathology and apoptosis in correlation with viral immunolabeling at different time points. Curionopolis and Itacaiunas viral antigens were first detected in the parenchyma of olfactory pathways at 2 and 3 days post-inoculation (dpi) and the first clinical signs were observed at 4 and 8 dpi, respectively. After Curionopolis infection, the mortality rate was 100% between 5 and 6 dpi, and 35% between 8 and 15 dpi after Itacaiunas infection. We identified CNS mice cell types both in vivo and in vitro and the temporal sequence of neuroanatomical olfactory areas infected by Itacaiunas and Curionopolis virus. Distinct virulences were reflected in the neuropathological changes including TUNEL immunolabeling and cytopathic effects, more intense and precocious after intracerebral or in vitro inoculations of Curionopolis than after Itacaiunas virus. In vitro studies revealed neuronal but not astrocyte or microglial cytopathic effects at 2 dpi, with monolayer destruction occurring at 5 and 7 dpi with Curionopolis and Itacaiunas virus, respectively. Ultrastructural changes included virus budding associated with interstitial and perivascular edema, endothelial hypertrophy, a reduced and/or collapsed small vessel luminal area, thickening of the capillary basement membrane, and presence of phagocytosed apoptotic bodies. Glial cells with viral budding similar to oligodendrocytes were infected with Itacaiunas virus but not with Curionopolis virus. Thus, Curionopolis and Itacaiunas viruses share many pathological and clinical features present in other rhabdoviruses but distinct virulence and glial targets in newborn albino Swiss mice brain

Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19

IntroductionMannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19.MethodsBlood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively.ResultsThe frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed.DiscussionThe results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19

Leprosy As a Complex Infection: Breakdown of the Th1 and Th2 Immune Paradigm in the Immunopathogenesis of the Disease

Leprosy is a chronic infectious disease whose evolution involves complex immune mechanisms of the host that influence the clinical presentation of the disease. For many years, the main interpretation of the host defense response was based on characterization of the established immune paradigm between T helper (Th) 1 and Th2 lymphocytes. However, with advances in the knowledge of immunology, new approaches have emerged along with the development of new immunological pathways that have changed the interpretation of the long-established paradigm of the polar forms of the disease, especially with the identification of new subtypes of T lymphocytes such as Th9, Th17, Th22, and Tregs. Thus, this review discusses the role of these new subtypes of T helper lymphocytes and how the development of the immune response of these cells modifies the pattern of the Th1/Th2 response in the immunopathogenesis of leprosy

Lacaziose (doença de Jorge Lobo): revisão e atualização

Lacaziose ou doença de Jorge Lobo é micose crônica, granulomatosa, causada por implantação traumática do fungo Lacazia loboi - patógeno não cultivável até o presente - nos tecidos cutâneo e subcutâneo, manifestando-se clinicamente por lesões nodulares queloidianas predominantes, envolvendo sobretudo pavilhões auriculares, face, membros superiores e inferiores, e não comprometendo as mucosas. A maioria dos casos humanos está registrada em países da América do Sul. Entretanto, a enfermidade apresenta aspectos epidemiológicos destacados, como o aparecimento em tribo Caiabi, no Brasil Central e em mamíferos não humanos, golfinhos de duas espécies (Tursiops truncatus e Sotalia guianensis) capturados na costa da Flórida (EUA), na foz do rio Suriname, na costa de Santa Catarina (Brasil), no golfo de Gasconha (baía de Biscaia-Europa), com manifestações cutâneas e achados histopatológicos muito similares às encontradas no homem. O artigo objetiva abordar características do fungo e sua taxonomia, e aspectos históricos, ecoepidemiológicos, clínicos, imuno-histoquímicos, histopatológicos, ultra-estruturais e terapêuticos

Immunohistochemical characterization of the M4 macrophage population in leprosy skin lesions

Abstract Background Since macrophages are one of the major cell types involved in the Mycobacterium leprae immune response, roles of the M1 and M2 macrophage subpopulations have been well defined. However, the role of M4 macrophages in leprosy or other infectious diseases caused by mycobacteria has not yet been clearly characterized. This study aimed to investigate the presence and potential role of M4 macrophages in the immunopathology of leprosy. Methods We analyzed the presence of M4 macrophage markers (CD68, MRP8, MMP7, IL-6, and TNF-α) in 33 leprosy skin lesion samples from 18 patients with tuberculoid leprosy and 15 with lepromatous leprosy by immunohistochemistry. Results The M4 phenotype was more strongly expressed in patients with the lepromatous form of the disease, indicating that this subpopulation is less effective in the elimination of the bacillus and consequently is associated with the evolution to one of the multibacillary clinical forms of infection. Conclusion M4 macrophages are one of the cell types involved in the microbial response to M. leprae and probably are less effective in controlling bacillus replication, contributing to the evolution to the lepromatous form of the disease

Deteccção do DNA de Mycobacterium leprae em secreção nasal Detección del ADN de Mycobacterium leprae en secreción nasal Detection of Mycobacterium leprae DNA in nasal swab

Estudos têm demonstrado alta sensibilidade da técnica da reação em cadeia de polimerase (PCR) na identificação do DNA do Mycobacterium leprae. Este estudo objetivou avaliar a sensibilidade da PCR na detecção do DNA do M. leprae em "swab" nasal de pacientes hansenianos e comparar os resultados com a baciloscopia e formas multibacilares (MBs) e paucibacilares (PBs). Foram coletadas amostras de secreção nasal de 24 pacientes hansenianos, conservadas em solução de lise um e dois. Os resultados da PCR foram altamente significativos (pLos estudios han demostrado una alta sensibilidad de la técnica de Reacción en Cadena de la Polimerasa (PCR) para identificar el ADN de Mycobacterium leprae. El objetivo del estudio fue evaluar la sensibilidad de la PCR en la detección de ADN de M. leprae en hisopo nasal de los pacientes hansenianos y comparar los resultados con la baciloscopía y las formas multibacilares (MBs) y paucibacilares (PBS). Se obtuvieron muestras de secreción nasal de 24 pacientes hansenianos, conservados en solución de lisis uno y dos. Los resultados de la PCR fueron muy significativas (p Studies have demonstrated high sensibility of the polimerase chain reaction (PCR) technique in the identification of the Mycobacterium leprae DNA . This study aimed to evalue the PCR sensibility at the detection of the M. leprae DNA in nasal swab of leprosy patients and to compare the results with the bacilloscopy and multibacillary (MBs) and paucibacilares (PBs) forms. Nasal secretion samples of 24 leprosy patients were collected, and were preserved in one and two lise's solution. The PCR results were highly significant (p <0.0000) and they revealed grater sensibility than bacilloscopy, in several clinical forms. Nevertheless, still different studies are necessary, testing new markers and preservatives, with the purpose of lifting up the sensibility of this technique, in nasal secretion samples

Protein profile of leprosy patients with plantar ulcers from the Eastern Amazon region

Abstract Background Studies investigating the nutritional status of patients with leprosy and plantar ulcers are sparse. Therefore, the objective of this study was to describe the protein profile of leprosy patients with plantar ulcers from the Eastern Amazon region. Methods A case record form was created for 75 patients with leprosy (31 with plantar ulcers and 44 without plantar ulcers) with the following data: sociodemographic characteristics, clinical form of leprosy, presence or absence of plantar ulcers, and nutritional assessment using anthropometry consisting of the measurement of body mass index, arm circumference, arm muscle circumference, and triceps skinfold. Levels of blood albumin, transferrin, and C-reactive protein (CRP) were also measured. Data regarding protein intake were obtained using a Food Frequency Questionnaire. Results Plantar ulcers occurred more frequently in male patients (67.7%), patients aged 40–49 years (mean ± SD: 47.3 ± 8.0 years), and patients receiving 300 or 600 USD (71.0%). The mean weight and height of patients were 71.6 ± 11.4 kg and 1.62 ± 0.1 m, respectively. High levels of CRP were detected in 51.6% of leprosy patients with plantar ulcers and only 9.1% of patients without plantar ulcers (P < 0.001). Nutritional depletion of transferrin was observed in 14.3% of patients with paucibacillary leprosy and 44.3% of patients with multibacillary leprosy (P = 0.0447). Most patients had normal levels of serum albumin (74.2% with plantar ulcers and 77.3% without plantar ulcers). Conclusions Most leprosy patients with plantar ulcers have normal levels of serum albumin and transferrin and high CRP levels, which indicates the presence of an inflammatory process. Our findings suggest the need to monitor patients with leprosy to prevent the occurrence of plantar ulcers and to provide adequate treatment for patients with existing plantar ulcers

Assessment of the treatment of chronic hepatitis C virus infection: a case series from a hospital in the Brazilian Amazon region

Universidade do Estado do Pará. Fundação Santa Casa de Misericórdia do Pará. Programa de Hepatopatias. Belém, PA, Brazil / Universidade Federal do Pará. Núcleo de Medicina Tropical. Laboratório de Imunopatologia. Belém, PA, Brazil.Universidade Federal do Pará. Núcleo de Medicina Tropical. Laboratório de Imunopatologia. Belém, PA, Brazil / Universidade do Estado do Pará. Centro de Ciências Biológicas. Belém, PA, Brazil.Universidade Federal do Pará. Belém, PA, Brazil / Universidade do Estado do Pará. Centro de Ciências Biológicas. Belém, PA, Brazil.Universidade Federal do Pará. Belém, PA, Brazil / Universidade do Estado do Pará. Centro de Ciências Biológicas. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil