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

Hepatic lesions in captive owl monkeys (Aotus infulatus) with ultrasonographic starry sky liver

Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (141398/2015-9).University of Sao Paulo. School of Veterinary Medicine and Animal Science. Department of Pathology. Sao Paulo, SP, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal Rural University of the Amazon. Institute of Animal Health and Production. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.University Sao Paulo. Faculty of Medicine. Department of Pathology. Sao Paulo, SP, Brazil.University of Sao Paulo. School of Veterinary Medicine and Animal Science. Department of Surgery. Sao Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.University of Sao Paulo. School of Veterinary Medicine and Animal Science. Department of Pathology. Sao Paulo, SP, Brazil.Background The "starry sky" (SK) liver is ultrasonographic pattern characterized by multiple hyperechogenic foci in hepatic parenchyma. The study aimed to characterize the microscopic hepatic lesions in captive owl monkeys with SK liver. Methods Thirty-seven clinically healthy owl monkeys had their liver scanned and 18 of them had liver biopsy. Animals with SK and peliosis hepatis (PH) were subjected to immunohistochemical and molecular screening for Bartonella spp. Results SK liver occurred in 59.4% (22/37) of the owl monkeys. Biopsied animals showed steatosis, hydropic degeneration, hemosiderosis, PH, and multifocal granulomatous hepatitis. Two monkeys had SK, granulomatous hepatitis, and PH which were negative for Bartonella spp. Conclusions PH and granulomatous hepatitis associated with hepatocellular degenerative lesions may present as hyperechoic nodular liver lesions consisted of SK liver; therefore, concomitant occurrence of two lesions or more contributed to the hepatic SK pattern among owl monkeys and such cases might be clinically monitored

<i>In Situ</i> Immune Response in Human Chromoblastomycosis – A Possible Role for Regulatory and Th17 T Cells

<div><p>Background</p><p>Chromoblastomycosis is a chronic fungal infection that affects skin and subcutaneous tissue. Lesions can be classified in tumorous, verrucous, cicatricial and plaque type. The cellular immune response in the severe form of the disease seems to correlate with a Th2 pattern of cytokines. The humoral immune response also seems to play a role. We intended to explore the populations of regulatory T cells and the Th17 pattern.</p><p>Methodology</p><p>Twenty-three biopsies of verrucous form were obtained from patients with clinical, culture and histopathological diagnostic of chromoblastomycosis, without treatment. It was performed an immunohistochemistry method to detect Foxp3, CD25, TGF-β, IL-6, IL-17 and IL-23.</p><p>Principal findings</p><p>IL-17 was the only cytokine with high expression in CBM when compared to normal skin. The expression of Treg cells, TGF- β, IL-6 and IL-23 were similar to normal skin.</p><p>Conclusions/Significance</p><p>The constitution of a local immune response with high expression of IL-17 and low expression of other cytokines could be at least in part, an attempt to help the immune system against fungal infection. On the other hand, high levels of local immune response mediated by Th17 profile could overcome the role of Treg cells. The inefficient immunomodulation as a consequence of the unbalance by Treg/Th17 cells seems to corroborate with the less effective immune response against fungi.</p></div

Upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in renal tissue in severe dengue in humans: Effects on endothelial activation/dysfunction

This study was partially supported by the National Institute of Science and Technology for Viral Haemorrhagic Fevers-INCT-FHV INCT-FHV. (MCT/CNPq/FNDCT/CAPES/FAPESPA No. 15/2008) process 573739/2008-0, CNPq process 501549/2003-0, and CNPq process 301641/2010-2.Universidade de São Paulo. Faculdade de Medicina. Laboratório da Disciplina de Patologia de Moléstias Transmissíveis. São Paulo, SP, Brasil / Instituto de Assistência Médica ao Servidor Público Estadual. Programa de Pós-Graduação em Ciências da Saúde. São Paulo, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina. Laboratório da Disciplina de Patologia de Moléstias Transmissíveis. São Paulo, SP, Brasil / Instituto de Assistência Médica ao Servidor Público Estadual. Programa de Pós-Graduação em Ciências da Saúde. São Paulo, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina. Laboratório da Disciplina de Patologia de Moléstias Transmissíveis. São Paulo, SP, Brasil.Hospital Guilherme Álvaro. Santos, SP, Brasil.Hospital Guilherme Álvaro. Santos, SP, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Muniz. Salvador, BA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade de São Paulo. Faculdade de Medicina. Laboratório da Disciplina de Patologia de Moléstias Transmissíveis. São Paulo, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina. Laboratório da Disciplina de Patologia de Moléstias Transmissíveis. São Paulo, SP, Brasil.Universidade Federal do Pará. Núcleo de Medicina Tropical. Belém, PA, Brasil.Universidade de São Paulo. Faculdade de Medicina. Laboratório da Disciplina de Patologia de Moléstias Transmissíveis. São Paulo, SP, Brasil / Instituto de Assistência Médica ao Servidor Público Estadual. Programa de Pós-Graduação em Ciências da Saúde. São Paulo, SP, Brasil.INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD

Comparative analysis among chromoblastomycosis, paracoccidioidomycosis and normal skin groups.

<p>Distribution of number of cells/mm² expressing Foxp3, CD25, TGF-β, IL-6, IL-23 and IL-17. Mann-Whitney test, * p<0.05.</p

Immunohistochemistry of representative chromoblastomycosis skin lesion.

<p>A: Nuclear expression of Foxp3 in regulatory T cells. B: expression of CD25 in lymphocytes of the inflammatory infiltrate. C: Low number of cells expressing TGF-β. D: Scarce presence of IL-6. E: Intense number of T cells with expression of IL-17 in the inflammatory infiltrate. F: Low number of cells expressing IL-23 distributed in the lesion. Streptavidin-biotin peroxidase, immunostaining in brown (×200 and inset ×400).</p

Chromoblastomycosis – Histopathology of skin lesions.

<p>A: epidermis presenting pseudocarcinomatous hyperplasia and acantosis (×40); B: presence of acantosis and intraepidermal microabscess (×100); C: dermal inflammatory infiltrate characterized by granulomatous response with giant cells, high number of fungal cells, eosinophils, macrophages and lymphocytes (×200) (hematoxylin-eosin).</p