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Chromoblastomycosis (CBM) is a chronic, progressive fungal disease of the skin and subcutaneous tissue caused by a group of dematiaceous fungi. Verrucous lesions present parasite-rich granulomas and predominance of a Th2 patterns of cytokines. The inflammasome constitutes a macromolecular protein complex that play a role in the activation of caspase 1 that cleaves pro-IL1β and pro-IL18, essential mediators of inflammation, and also activates pyroptosis. We intended to explore the presence and a possible role of inflammasome elements in cutaneous human lesions in CBM, considering the expression of IL1β, IL18, caspase 1, NLRP1, and also RIPK3, a key downstream component of necroptosis signaling. 35 skin biopsies of cutaneous lesions of verrucous form of CBM and 10 biopsies from normal skin were selected. The diagnosis was based on histological and clinical analysis. An immunohistochemical protocol was performed. The histopathological analysis evidenced epidermis with hyperkeratosis, irregular acanthosis, and micro abscesses. The dermis presented suppurative granulomas and inflammatory infiltrate composed by giant cells, macrophages, epithelioid cells, lymphocytes, and some eosinophils. Positive cells were distributed in the inflammatory infiltrate, with an increased number of cells expressing caspase 1, IL1β and IL18. Cells expressing RIPK3 and NLRP1 were less frequent. The intense presence of caspase 1, IL1β and IL18, allied to NLRP1 expression, suggest that inflammasome and pyroptosis could play a role in the immune response against fungal agents of CBM. Our results, allied to data from literature, could suggest that inflammasome-mediated response and pyroptosis could be a target to be explored to decrease CBM lesions.

Fibrosis is a common pathophysiological response of many tissues and organs subjected to chronic injury. Despite the diverse aetiology of keloid, lacaziosis and localized scleroderma, the process of fibrosis is present in the pathogenesis of all of these three entities beyond other individual clinical and histological distinct characteristics. Fibrosis was studied in 20 samples each of these three chronic cutaneous inflammatory diseases. An immunohistochemical study was carried out to explore the presence of α-smooth muscle actin (α-SMA) and vimentin cytoskeleton antigens, CD31, CD34, Ki67, p16; CD105, CD163, CD206 and FOXP3 antigens; and the central fibrotic cytokine TGF-β. Higher expression of vimentin in comparison to α-SMA in all three lesion types was found. CD31- and CD34-positive blood vessel endothelial cells were observed throughout the reticular dermis. Ki67 expression was low and almost absent in scleroderma. p16-positive levels were higher than ki67 and observed in reticular dermis of keloidal collagen in keloids, in collagen bundles in scleroderma and in the external layers of the granulomas in lacaziosis. The presence of α-actin positive cells and rarely CD34 positive cells, observed primarily in keloids, may be related to higher p16 antigen expression, a measure of cell senescence. Low FOXP3 expression was observed in all lesion types. CD105-positive cells were mainly found in perivascular tissue in close contact with the adventitia in keloids and scleroderma, while, in lacaziosis, these cells were chiefly observed in conjunction with collagen deposition in the external granuloma layer. We did not find high involvement of CD163 or CD206-positive cells in the fibrotic process. TGF-β was notable only in keloid and lacaziosis lesions. In conclusion, we have suggested vimentin to be the main myofibroblast general marker of the fibrotic process in all three studied diseases, while endothelial-to-mesenchymal transition (EndoMT) and mesenchymal stem cells (MSCs) and M2 macrophages may not play an important role.

This is an updated report of the work of the JPEG Committee formed by the International Telecommunication Union (ITU), the International Organization for Standardization (ISO), and the International Electrotechnical Commission (IEC), known as the Joint Photographic Experts Group (JPEG). A detailed introduction to JPEG's work was already presented in Ref. 1. In this report, the focus is more on updated work since 2020 and on new work items and explorations.

Arboviruses such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV) presenting wide global dissemination and the pathogenic profile developed in infected individuals, which develop from nonspecific clinical conditions to severe forms, characterized by the promotion of significant lesions in different organs of the harborer, culminating in multiple organ dysfunction. To characterize, quantify, and compare the patterns of histopathological alterations in human liver samples from patients with yellow fever (YF), dengue fever (DF), and chikungunya fever (CF). Analytical cross-sectional study by histopathological analysis with 70 samples of liver patients, collected from 2000 to 2017, with confirmed laboratory diagnosis who died due to infection and complications by the YF, DF, and CF. Of the histopathological findings in human liver samples there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analyzed, among the arboviruses studied, the hepatic involvement in cases of YF showed greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis and apoptosis were classified as degree of tissue damage from severe to very severe. The pathological abnormalities associated with infection by YFV, DENV, and CHIKV showed predominance of changes in the midzonal area. We also noted that in among of the arboviruses studied, liver involvement in cases of YFV infection was more intense.

Lacaziosis is a cutaneous chronic mycosis caused by Lacazia loboi. Macrophages are important cells in the host immune response in fungal infections. The macrophage population exhibits strong plasticity that varies according to the stimuli in the microenvironment of lesions M1 profile promotes a Th1 pattern of cytokines and a microbicidal function and M2 is related to Th2 cytokines and immunomodulatory response. We investigated the population of M1 and M2 polarized macrophages in human cutaneous lesions. A total of 27 biopsies from human lesions were submitted to an immunohistochemistry protocol using antibodies to detect M1 and M2 macrophages (Arginase-1, CD163, iNOS, RBP-J and cMAF). We could observe high number of cells expressing Arginase1, CD163 and c-MAF that correspond to elements of the M2 profile of macrophage, over iNOS and RBP-J (elements of the M1 profile). The results suggest a predominant phenotype of M2 macrophages, which have an immunomodulatory role and probably contributing to chronicity of Lacaziosis. Electronic supplementary material The online version of this article (10.1007/s11046-020-00450-z) contains supplementary material, which is available to authorized users.

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade de S?o Paulo. Departamento de Patologia. Faculdade de Medicina. S?o Paulo, SP, Brazil. Funda??o Oncocentro de S?o Paulo. S?o Paulo, SP, Brazil. Faculdade de Medicina de S?o Jos? Do Rio Preto. S?o Paulo, SP, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal Do Cear?. Drug Research and Development Center. Laboratory of Pharmacogenetics. Fortaleza, CE, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Dengue virus causes dengue hemorrhagic fever (DHF) and has been associated to fatal cases worldwide. The liver is one of the most important target tissues in severe cases, due to its intense viral replication and metabolic role. microRNAs role during infection is crucial to understand the regulatory mechanisms of DENV infection and can help in diagnostic and anti-viral therapies development. We sequenced the miRNome of six fatal cases and compared to five controls, to characterize the human microRNAs expression profile in the liver tissue during DHF. Eight microRNAs were differentially expressed, including miR-126-5p, a regulatory molecule of endothelial cells, miR-122-5p, a liver specific homeostasis regulator, and miR-146a-5p, an interferon-regulator. Enrichment analysis with predicted target genes of microRNAs revealed regulatory pathways of apoptosis, involving MAPK, RAS, CDK and FAS. Immune response pathways were related to NF- kB, CC and CX families, IL and TLR. This is the first description of the human microRNA and isomicroRNA profile in liver tissues from DHF cases. The results demonstrated the association of miR-126-5p, miR-122-5p and miR-146a-5p with DHF liver pathogenesis, involving endothelial repair and vascular permeability regulation, control of homeostasis and expression of inflammatory cytokines.

This study presents a single center experience with livedoid vasculopathy (LV). A rare disease that can lead to severe quality of life impairment. Characterize clinical data of LV patients at the Dermatology Division at the University of Sao Paulo. A retrospective and transversal study was conducted, from 1 January 2005 to 31 December 2019. About 75 patients diagnosed as LV and confirmed by skin biopsy were included. Epidemiology, clinical appearance, histopathology data, and treatment history were observed. There were 78.66% Caucasian women, with a mean age of 39.9 years. Frequent cutaneous manifestations were ulcers, atrophic blanche-like scars, hyperpigmentation, purpuras, telangiectasias, and livedo racemosa. Pain, pruritus, and hypoesthesia were the main symptoms. After treatment, almost 40% of cases relapsed during spring and summer months. About 66% of cases had thrombophilia factors associated, such as high levels of lipoprotein(a). Frequent treatments included acetylsalicylic acid, pentoxifylline, and diosmin with hesperidin. Not being a prospective study. This research provides useful data on Latin American LV patients, indicating multifactorial conditions involved in LV pathogenesis. An extensive work-up including autoimmune laboratory tests, thrombophilia factors, and other conditions associated with venous stasis should be part of LV investigation and controlled to improve treatment response.

Cryptococcosis is the second most common invasive fungal infection reported in renal transplant recipients. Tissue granulomatous inflammation is necessary to contain Cryptococcus infection. This study aims to analyze the granuloma patterns and in situ expression of regulatory T (Treg) immune response in tissue samples from 12 renal transplant recipients with cryptococcosis. Fungal isolates were molecularly identified as Cryptococcus neoformans species complex. A detailed characterization of granulomas in tissue samples from 12 kidney transplant recipients with cryptococcosis was described by checking six lung and six skin biopsies by conventional histology and for immunohistochemical detection of CD4 and Treg markers: forkhead box P3 (FoxP3), interleukin (IL)-10 and transforming-growth factor (TGF)-β. Granulomas were classified as compact, loose or mixed. Patients with mixed (n = 4) and compact (n = 3) granulomatous inflammation patterns were associated with a better prognosis and presented a higher number of CD4+FoxP3+T cells compared to the group of patients with loose granulomas. In counterpart, three out of five patients with loose granulomas died with cryptococcosis. We suggest that Treg may have a protective role in the tissue response to Cryptococcus infection given its association with compact and mixed granulomas in patients with better clinical outcomes.

Coronavirus disease (COVID-19) pandemic presents several dermatological manifestations described in the present indexed literature, with around 700 cases reported until May 2020, some described as urticaria or urticarial rashes. Urticaria is constituted by evanescent erythematous-edematous lesions (wheals and flare), which does not persist in the same site for more than 24 to 48 hours and appears in other topographic localization, resolving without residual hyper pigmentation. During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, some cytokines are synthesized, including Interferon (IFN) type I, TNF-α, and chemokines which may induce mast cells (MCs) and basophils degranulation by mechanisms similar to the autoinflammatory monogenic or polygenic diseases. In this article, we discuss the spectrum of the urticaria and urticarial-like lesions in the COVID-19's era, besides other aspects related to innate and adaptative immune response to viral infections, interactions between dermal dendritic cells and MCs, and degranulation of MCs by different stimuli. Plasmacytoid dendritic cells share, in allergic patients, expression of the high-affinity IgE receptors on cell membranes and demonstrated a low pattern of type I IFN secretion in viral infections. We discuss the previous descriptions of the effects of omalizumab, a monoclonal antibody directed to IgE and high-affinity IgE receptors, to improve the IFN responses and enhance their antiviral effects.

Mast cells and basophils interact with various cells in the urticaria lesion microenvironment, such as macrophages,.which form an essential component of innate immunity, and are involved in numerous functions including protein secretion. Objective: The aim of the present study was to characterize the macrophage phenotype in urticarial lesions of patients with chronic spontaneous urticaria (CSU) nonresponsive to antihistamines at optimized doses. And compare the phenotype with clinical and laboratory parameters such as age, gender, urticaria time, C-reactive protein (CRP), and total serum IgE, and autologous serum skin test (ASST). Methods: Twenty-eight patients with CSU refractory to antihistamines were included in the study. Epidemiological data, C-reactive protein, D-dimers, basophils in peripheral blood, and total serum IgE and ASST were assessed. The mannose receptor (CD206), CD163, CMAF, and pSTAT 1 were used to characterize the M1/M2 macrophage subpopulations. The immunolabeled cells per square millimeter were manually enumerated at a 400× magnification in 12 optical fields via light microscopy. Results: A predominance of M2 macrophages was seen in CSU patients. Statistical differences were observed between the CD206 marker and the disease course. No correlation was found between biomarkers and macrophage populations. Expression of CMAF was significantly higher in the patient sample compared to that in the control skin (patients without history of urticaria; p-value < 0.001). Conclusion: M2 macrophages were seen with significantly higher CMAF expression, which indicates macrophage activation in patients with CSU. CD206 expression was inversely correlated with disease time.

Summary The SARS‐Cov‐2 is a single‐stranded RNA virus composed of 16 non‐structural proteins (NSP 1‐16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid‐19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid‐19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a ‘cytokine storm’. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D‐dimer, lactic dehydrogenase, reactive‐C‐protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug‐related intertriginous and flexural exanthema. This review describes the complexity of Covid‐19, its pathophysiological and clinical aspects.

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.

Cutaneous leishmaniasis (CL) is caused by the bite of the infected sand fly, which inoculates parasites of Leishmania spp and triggers an immune response. An exacerbated cutaneous inflammatory response is crucial for controlling parasite burden but can also promote tissue damage. This study aimed to characterize the populations of natural killer (NK), CD57+, CD4+, and CD8+ T cells, CD20+ B cells, as well as CD68+ macrophages, in biopsies of ulcerated CL lesions, and quantify the production of perforin+, grazyme B+, interleukin 1 beta (IL-1β+) and Tumor Necrosis Factor (TNF-α+ cells). We then correlated these parameters with necrosis, inflammation and the number of amastigotes. CD4+ T cells were positively correlated to the extent of inflammation, B cells and IL-1β+ were associated with the extent of necrosis, CD68+ macrophages and perforin were correlated with the number of amastigotes, and CD57+ NK cells was correlated to CD68+ macrophages and amastigotes. In sum, the finding suggests that the production of cytotoxic granules and cytokines by inflammatory cells contributes to tissue damage in CL lesions.

BACKGROUND Histoid leprosy (HL) is a rare form of lepromatous leprosy, characterized by hyperchromic indurated nodules above normal skin. Its main histopathological aspect is spindle cells. Because it may simulate other aspects, such as dermatofibroma and neurofibroma, histoid leprosy poses itself as a diagnostic challenge. METHODS This is a retrospective study with all patients having been selected from the leprosy clinic of the Hospital das Clinicas da Universidade de Sao Paulo from 2006 to 2016. RESULTS There were 12 patients in this study, eight in the histoid group and four in the lepromatous leprosy group. The prevalence of HL was 1.12% in all leprosy subjects. All individuals from HL group were "de novo" cases, and the histopathological analysis of skin lesions presented spindle cells generating a storiform pattern. Immunohistochemistry for CD68, vimentin, and anti-BCG were positive in all 12 cases. Factor XIIIa was visualized only in the papillary dermis, and S100 protein was negative in all biopsies. Smooth-muscle actin was present in 62.5% of the HL samples. CONCLUSION The prevalence of HL was similar to previous reports. However, all histoid patients were "de novo" cases, differing from published studies. Fusocellular macrophage transformation could be explained by the differences in cytoskeleton proteins expressed in histoid lesions in comparison to other leprosy variants, with emphasis on vimentin and smooth muscle actin.

Background and Aim Although the esophagus is a common site of opportunistic infection in AIDS patients, little is known about the impact of HIV as well as opportunistic infection in the esophageal mucosa. Our aim is to analyze the esophageal immune profile in HIV+ patients with different immunological status with and without the opportunistic Candida infection. Methods Immunohistochemistry to CD4+ and CD8+ T-cells, γ-interferon, transforming growth factor-β, interleukin (IL)-4, IL-6, IL-13, and IL-17 was performed in esophageal samples of 40 chronically HIV+ patients under highly active antiretroviral therapy (16 with Candida esophagitis, 12 virologically non-supressed with blood CD4 count 500; the latter two groups without esophageal candidiasis). The controls were 12 HIV-negative healthy individuals. Results Esophageal CD4+ T-cell expression in HIV+ patients did not differ from the control group (P = 0.50). Mucosal CD8+ T-cell expression was significantly increased in HIV+ patients (P = 0.0018). Candida esophagitis and virologically non-supressed HIV+ patients with CD4 500. IL-4 and IL-13 were similar to the control group. Conclusion In contrast to CD8+ T-cell expression, esophageal CD4+ T-cell expression does not reflect the HIV+ patient's immunological status. T-helper 17 (Th17) response seems to play a role in the esophageal mucosa of virologically non-supressed HIV+ patients with blood CD4

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 S?o Paulo. Faculdade de Medicina. Laborat?rio da Disciplina de Patologia de Mol?stias Transmiss?veis. S?o Paulo, SP, Brasil / Instituto de Assist?ncia M?dica ao Servidor P?blico Estadual. Programa de P?s-Gradua??o em Ci?ncias da Sa?de. S?o Paulo, SP, Brasil. Universidade de S?o Paulo. Faculdade de Medicina. Laborat?rio da Disciplina de Patologia de Mol?stias Transmiss?veis. S?o Paulo, SP, Brasil / Instituto de Assist?ncia M?dica ao Servidor P?blico Estadual. Programa de P?s-Gradua??o em Ci?ncias da Sa?de. S?o Paulo, SP, Brasil. Universidade de S?o Paulo. Faculdade de Medicina. Laborat?rio da Disciplina de Patologia de Mol?stias Transmiss?veis. S?o Paulo, SP, Brasil. Hospital Guilherme ?lvaro. Santos, SP, Brasil. Hospital Guilherme ?lvaro. Santos, SP, Brasil. Funda??o Oswaldo Cruz. Centro de Pesquisa Gon?alo Muniz. Salvador, BA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade de S?o Paulo. Faculdade de Medicina. Laborat?rio da Disciplina de Patologia de Mol?stias Transmiss?veis. S?o Paulo, SP, Brasil. Universidade de S?o Paulo. Faculdade de Medicina. Laborat?rio da Disciplina de Patologia de Mol?stias Transmiss?veis. S?o Paulo, SP, Brasil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Bel?m, PA, Brasil. Universidade de S?o Paulo. Faculdade de Medicina. Laborat?rio da Disciplina de Patologia de Mol?stias Transmiss?veis. S?o Paulo, SP, Brasil / Instituto de Assist?ncia M?dica ao Servidor P?blico Estadual. Programa de P?s-Gradua??o em Ci?ncias da Sa?de. S?o 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.

Dermatophytosis is a cutaneous mycosis caused by a plethora of keratinophilic fungi, but Trichophyton rubrum is the most common etiological agent. Despite its high prevalence worldwide, little is known about the host defense mechanisms in this infection, particularly the in situ immune response. Using an immunohistochemistry approach, we investigated the density of CD1a+, factor XIIIa+ and CD68+ cells in the skin of dermatophytosis patients. Langerhans cells (CD1a+ cells) were significantly decreased in the epidermis of patients, both in affected and unaffected areas. In the dermis, however, no differences in the density of macrophages (CD68+ cells) and dermal dendrocytes (factor XIIIa+ cells) were observed. These results suggest that the decreased number of Langerhans cells may be a risk factor for development of dermatophytosis.

Leprosy is frequently complicated by the appearance of reactions that are difficult to treat and are the main cause of sequelae. We speculated that disturbances in regulatory T-cells (Tregs) could play a role in leprosy reactions. We determined the frequency of circulating Tregs in patients with type 1 reaction (T1R) and type 2 reaction (T2R). The in situ frequency of Tregs and interleukin (IL)-17, IL-6, and transforming growth factor beta (TGF)-β-expressing cells was also determined. T2R patients showed markedly lower number of circulating and in situ Tregs than T1R patients and controls. This decrease was paralleled by increased in situ IL-17 expression but decreased TGF-β expression. Biopsies from T1R and T2R patients before the reaction episodes showed similar number of forkhead box protein P3 + (FoxP3+) and IL-17+ cells. However, in biopsies taken during the reaction, T2R patients showed a decrease in Tregs and increase in IL-17+ cells, whereas T1R patients showed the opposite: Tregs increased but IL-17+ cells decreased. We also found decreased expansion of Tregs upon in vitro stimulation with Mycobacterium leprae and a trend for lower expression of FoxP3 and the immunosuppressive molecule cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in T2R Tregs. Our results provide some evidence to the hypothesis that, in T2R, downmodulation of Tregs may favor the development of T-helper-17 responses that characterize this reaction.

Mucosal lesions of paracoccidioidomycosis (PCM) are frequently described and clinically important. Macrophages are classified as M1 or M2. M1 are proinflammatory and M2 are related to chronicity. Dectin-1 recognizes β-glucan and plays an important role against fungal cells. The objective was to verify the presence of M1, M2, and dectin-1 and a possible correlation with Th1/Th2 cytokines in mucosal PCM lesions. In sum, 33 biopsies of oral PCM were submitted to histological and immunohistochemistry analysis, and positive cells were quantified. Eleven biopsies were characterized by compact granulomas (G1), 12 with loose granulomas (G2), and 10 with both kind of granulomas (G3). pSTAT-1 was equally increased in the three groups. G1 was characterized by an increased number of CD163+ macrophages. G2 presented similar number of arginase 1, iNOS, and CD163 expressing cells. G3 presented an increased number of cells expressing arginase 1 and CD163 over iNOS. G1 and G3 presented high number of cells expressing interferon (IFN)-γ; interleukin (IL) 5 was increased in G2 and G3; the expression of IL10 was similar among the three groups, and the expression of tumor necrosis factor (TNF)-α was higher in G3. G1 correlates to Th1 cytokines and pSTAT-1 and G2 correlates to Th2 cytokines. G3 presents both kinds of cytokines. We could not associate the expression of arginase-1, CD163, iNOS, and dectin-1 with the pattern of cytokines or kind of granuloma.

Trypanosoma cruzi infection stimulates inflammatory mediators which cause oxidative stress, and the use of antioxidants can minimize the sequelae of Chagas disease. In order to evaluate the efficacy of vitamin C in minimizing oxidative damage in Chagas disease, we orally administered ascorbic acid to Swiss mice infected with 5.0 × 104 trypomastigote forms of T. cruzi QM2 strain. These animals were treated for 60 days to investigate the acute phase and 180 days for the chronic phase. During the acute phase, the animals in the infected and treated groups demonstrated lower parasitemia and inflammatory processes were seen in more mice in these groups, probably due to the higher concentration of nitric oxide, which led to the formation of peroxynitrite. The decrease in reduced glutathione concentration in this group showed a circulating oxidant state, and this antioxidant was used to regenerate vitamin C. During the chronic phase, the animals in the infected and treated group showed a decrease in ferric reducing ability of plasma and uric acid concentrations as well as mobilization of bilirubin (which had higher plasma concentration), demonstrating cooperation between endogenous non-enzymatic antioxidants to combat increased oxidative stress. However, lower ferrous oxidation in xylenol orange concentrations was found in the infected and treated group, suggesting that vitamin C provided biological protection by clearing the peroxynitrite, attenuating the chronic inflammatory process in the tissues and favoring greater survival in these animals. Complex interactions were observed between the antioxidant systems of the host and parasite, with paradoxical actions of vitamin C.