Characterization of the Th17 profile immune response in cases of human rabies transmitted by dogs and its interference in the disease pathogenesis.

The Th17 profile immune response is influenced by the presence of cytokines such as IL-1, IL-6, TGF-ß, IL-17, and IL-23. We sought to characterize the Th17 profile in CNS samples from human rabies cases transmitted by dogs and examine its possible influence on disease pathogenesis. We observed a high expression of TGF-ß, followed by IL-23, IL-17 and IL-6, and a low expression of IL-1ß and IFN-γ. Those results suggest the participation of Th17 in rabies virus neuroinfection transmitted by dogs. IL-23 probably plays a role in maintaining the Th17 profile, but it can also interfere with the establishment of the Th1 profile and viral clearance.

Paradoxical effects of vitamin C in Chagas disease.

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.

Detection of Toxoplasma gondii in two southern Wooly spider monkeys (Brachyteles arachnoides-Geoffroy, 1806) from the Rio de Janeiro primate center, Brazil.

BACKGROUND: Toxoplasmosis led to the death of two Brachyteles arachnoides, an endangered atelid. METHODS: The diagnosis was established by necropsy, histopathological, immunohistochemical and ultrastructural changes. RESULTS: The analysis confirms the presence of Toxoplasma gondii. CONCLUSIONS: This report contributes to the development of protocols for health surveillance on maintenance and conservation of southern muriquis.

Malakoplakia after renal transplantation in the current era of immunosuppressive therapy: case report and literature review.

Malakoplakia is a rare chronic granulomatous disease of unknown cause. It is thought to be caused by an acquired bactericidal defect of macrophages. Malakoplakia is associated with chronic infections and immunosuppression. Although it occurs mainly in the urinary tract, it has already been reported in almost every organ system. The isolation of bacteria, especially Escherichia coli, is common in malakoplakia patients. Here, we present a case of primary cutaneous malakoplakia in a kidney transplant recipient who had been taking prednisone, tacrolimus, and mycophenolate. Culture of a lesion grew Burkholderia cepacia complex. Treatment with high doses of trimethoprim-sulfamethoxazole was successful. We also present a systematic review of the literature, identifying 4 previously reported cases of malakoplakia after renal transplantation under similar immunosuppressive therapy, most occurring in the urinary tract or perineum and following benign courses to cure. Data in the literature suggest that malakoplakia has become even rarer since changes were made in the immunosuppressive therapy employed after kidney transplantation.

Respiratory syncytial virus (RSV) pneumonia in a southern muriqui (Brachyteles arachnoides).

BACKGROUND: An adult male Brachyteles arachanoides, kept in captivity since 1990, was found dead without apparent clinical evidence. METHODS: Necropsy report, histopathology, immunohistochemistry, and ultrastructural examination were conducted. RESULTS: Pulmonary syncytial cells were positive for respiratory syncytial virus (RSV), and ultrastructural examination revealed viral particles inside macrophages compatible with the Paramyxoviridae family. CONCLUSIONS: Muriquis are susceptible to RSV pneumonia followed by respiratory distress syndrome and death.

Are the severe injuries of cutaneous leishmaniasis caused by an exacerbated Th1 response?

American tegumentary leishmaniasis (ATL) is a disease whose clinical features are strongly related to the type of immune response it induces. Herein we report an atypical presentation of cutaneous leishmaniasis in a woman with a severe and extensive sore located in her leg, and we describe the differences between the usual local immune response in ATL and the local immune response in this patient. We observed an intense inflammatory response characterized by Th1 cells and cytokines with conspicuous expression of Toll-like receptor 3 (TLR-3). Few parasites were present, but there was an extensive tissue damage. We also discuss the immunological factors that could be related to the atypical presentation.

The expression of TLR9 in human cutaneous leishmaniasis is associated with granuloma.

The Toll-like receptor (TLR) signalling pathway is the first system that defends against Leishmania. After recognising Leishmania as nonself, TLRs trigger NF-κB expression.NF-κB proceeds to the nucleus and promotes the transcription of pro-inflammatory cytokines. TLR9 is thus an important factor in the induction of an effective immune response against Leishmania. We examined the pattern of TLR9 expression in 12 patients with cutaneous leishmaniasis caused by Leishmania braziliensis detected by polymerase chain reaction. Normal skin was analysed as a negative control. TLR9 expression was examined in the dermis and epidermis by immunohistochemical analysis of paraffin-embedded biopsy tissue. TLR9 expression was primarily observed in the granuloma. The protein was detected in a few cells in the dermis. A lower expression level was detected in the epidermis of patients with leishmaniasis when compared with normal skin. The presence of TLR9 in the skin of patients with cutaneous leishmaniasis is associated with granuloma and expressed by macrophages.

Tissue and serum immune response in chronic hepatitis C with mild histological lesions.

The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro and anti-inflammatory activity. We investigated the expression of inflammatory cells and cytokines in the liver and serum of 51 chronically HCV infected patients and compared them to data from two sets of normal controls: 51 healthy blood donors and 33 liver biopsies of healthy liver donors. We also assessed the relationship between selected cytokines and cell populations in hepatic compartments and the disease stage. Compared with controls, hepatitis C patients had a greater expression of portal TNF-alpha, TGF-beta and CD4(+) and acinar IFN-gamma, TNF-alpha, IL-1beta and IL-4, as well as a higher serum concentration of IL-2, IL-10 and TGF-beta. Significant positive correlations were found between portal CD4+ and TNF-alpha, portal CD8(+) and TGF-beta, portal CD45(+)RO and TNF-alpha, acinar CD45(+)RO and IFN-gamma and acinar CD57(+) and TGF-beta. In conclusion, we have shown that (i) in this sample of predominantly mild disease, the immune response was associated with a pro-inflammatory response pattern, (ii) CD4(+) T-lymphocytes played a major role in orchestrating the immune response and (iii) these events primarily took place in the portal space.

Leptospirosis pulmonary haemorrhage syndrome is associated with linear deposition of immunoglobulin and complement on the alveolar surface.

Leptospirosis is a zoonotic infection associated with severe diseases such as leptospirosis pulmonary haemorrhage syndrome (LPHS). The cause of pulmonary haemorrhage is unclear. Understanding which mechanisms and processes are involved in LPHS will be important in treatment regimens under development for this life-threatening syndrome. In the present study, we evaluated 30 lung specimens from LPHS patients and seven controls using histology and immunohistochemistry (detection of IgM, IgG, IgA and C3) in order to describe the pathological features associated with this syndrome. Immunoglobulin deposits were detected on the alveolar surface in 18/30 LPHS patients. Three staining patterns were observed for the immunoglobulins and C3 in the lung tissues of LPHS patients: AS, delicate linear staining adjacent to the alveolar surface, which was indicative of a membrane covering the luminal surface of type I and II pneumocyte cells; S, heterogeneous staining which was sporadically distributed along the alveolar septum; and IA, weak, focal intra-alveolar granular staining. Human LPHS is associated with individual and unique histological patterns that differ from those of other causes of pulmonary haemorrhage. In the present study, it was found that the linear deposition of immunoglobulins (IgA, IgG and IgM) and complement on the alveolar surface may play a role in the pathogenesis of pulmonary haemorrhage in human leptospirosis.

Unusual manifestations of tegumentary leishmaniasis in AIDS patients from the New World.

BACKGROUND: Comorbidity from tegumentary leishmaniasis and AIDS is poorly characterized. OBJECTIVES: To describe a series of patients coinfected with Leishmania and human immunodeficiency virus (HIV). METHODS: Clinical records from patients were analysed by demographic data, clinical manifestations, diagnoses, treatments and outcomes. RESULTS: Fifteen cases of AIDS/tegumentary leishmaniasis were found. The diagnosis of leishmaniasis was confirmed by the detection of Leishmania amastigotes or antigens from the cutaneous or mucosal lesions. The mean CD4+ T-cell count was 84 cells mm(-3) (range 8-258) and all patients were classified as having AIDS according to the Centers for Disease Control and Prevention. A wide range of manifestations was found, varying from a single ulcer to multiple and polymorphic lesions. Mucosal lesions were present in 80% and cutaneous lesions in 73% of patients (53% with mucocutaneous form), disseminated lesions in 60% and genital lesions in 27% of patients. All patients received anti-Leishmania therapy and 53% showed relapses. Sixty-seven per cent received highly active antiretroviral therapy but showed no difference in outcomes and relapses compared with those not using medication. Forty per cent died during the study period. In these patients, the anti-Leishmania antibody and Montenegro skin test were useful in the diagnosis of leishmaniasis, probably because leishmaniasis preceded immunosuppression due to HIV infection. CONCLUSIONS: Clinical manifestations of tegumentary leishmaniasis in HIV-infected patients are diverse. Our data emphasize possible unusual manifestations of this disease in HIV-infected patients, particularly in severely immunosuppressed cases (< 200 CD4+ cells mm(-3)).

A quantitative and morphometric study of mast cells in cutaneous leishmaniasis.

Background Mast cells (MCs) are related with healing process in chronic inflammatory diseases, although in cutaneous leishmaniasis (CL) its importance is unknown. The aim of this study was to determine the correlation of MC with clinical findings in patients with the localized form of CL. Methods A cohort of 85 patients with CL was evaluated. MCs count was performed in pre-treatment biopsies and correlation with clinical findings and Leishmania species determined by PCR were performed. Results The MCs count in patients with CL caused by Leishmania (V.) braziliensis was 14.3 +/- 9.8 cells/mm(2), and 7.0 +/- 6.5 cells/mm(2) in patients with L. (L.) amazonensis (P < 0.05). The linear regression of MCs count with the age showed a tendency of cell number decreasing, according to ageing of the patient (r2 = 0.05; P < 0.05). The association of disease's duration and MCs count was positive (r2 = 0.11; P < 0.05). There was not any association of MCs count with number of lesions neither with Leishmania antigen expression. The MCs count was higher in patients with earlier healing after treatment (P < 0.05). Conclusion MC can be important in CL and related with healing lesion.

Histopathology of mast cells and cytokines during healing of human mucosal leishmaniasis.

Mast cells (MCs) are associated with chronic inflammatory diseases. However, there is no study evaluating the importance of MCs in the mucosal leishmaniasis (ML). The aim of this study was to quantify the most important cytokines associated with mucosal leishmaniasis, before and after disease treatment, correlating with the healing. A cohort of 12 patients with ML was evaluated, and biopsies were taken before and after the treatment. A quantitative estimation of MCs and some cytokines was analysed by density of the labelled cells through immunohistochemistry. The MCs count in the tissue from patients with ML before treatment showed a mean of 29.3 +/- 37.9 cells/mm(2). The MCs count in patients with ML after healing decreased to 14.8 +/- 23.9 cells/mm(2). There was an inverse relation of MCs with IFN-gamma and IL-4 expression (r2 = 29.4 and r2 = 22.3 with P < 0.05). The expression of IL-10 and TNF-alpha was not related with MCs count. MCs decrease after treatment associated with decrease of IL-4 and IFN-gamma. The explanations of cytokine correlation are discussed in the article.

The effects of human herpesvirus 8 infection and interferon-gamma 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. OBJECTIVES: To evaluate the HHV-8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS-associated KS (AIDS-KS). METHODS: We performed a quantitative immunohistochemical study of cells expressing HHV-8 latency-associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)-gamma in skin lesions from patients with CKS and AIDS-KS (with or without highly active antiretroviral therapy, HAART). RESULTS: CKS showed higher LANA expression compared with AIDS-KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS-KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN-gamma, as shown by double immunostaining. AIDS-KS presented low numbers of IFN-gamma-expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS. CONCLUSIONS: Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T-cell involvement associated with IFN-gamma, an environment of immune response-modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV-8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.

Immunopathology of the duodenal mucosa of HIV-positive patients during combined antiretroviral therapy.

The objective of the present study was to evaluate the duodenal mucosa of HIV-infected patients during antiretroviral therapy. This was an observational study conducted on HIV-positive patients and a control group. Group 1 comprised 22 HIV-negative individuals while 38 HIV-positive individuals were classified according to the CDC 1993 classification into group 2 (A1 or A2) or group 3 (B2, A3, B3, C2, C3). All subjects were submitted to upper gastrointestinal endoscopy with duodenal biopsies. Qualitative, semi-quantitative and quantitative histological analyses were performed. Results were considered significant when P < 0.05. A higher prevalence of inflammatory infiltrate and eosinophilia was observed in the HIV group, together with a reduction in mucosal CD4+ lymphocyte (L) counts [median (lower-upper quartiles), 12.82 (8.30-20.33), 6.36 (1.75-11.66) and 1.75 (0.87-3.14) in groups 1, 2 and 3, respectively] which was not correlated with disease stage. The extent of CD4+L count reduction was similar in blood and duodenal mucosa. Normal CD8+L and CD45RO+L counts, and normal numbers of macrophages and antigen-presenting cells were also found in the HIV patients. The cytokine pattern did not differ among groups. Tissue HIV, assessed by p24 antigen, correlated with a higher CD45RO+L count (77.0 (61-79.8) and 43.6 (31.7-62.8) in p24+ and p24-, respectively, P = 0.003), and IL-4 positivity (100 and 48.2% in p24+ and p24-, respectively, P = 0.005). The duodenal mucosa of HIV+ patients showed a relatively preserved histological architecture. This finding may be characteristic of a population without opportunistic infections and treated with potent antiretroviral therapy, with a better preservation of the immune status.

Immunopathology of the duodenal mucosa of HIV-positive patients during combined antiretroviral therapy

The objective of the present study was to evaluate the duodenal mucosa of HIV-infected patients during antiretroviral therapy. This was an observational study conducted on HIV-positive patients and a control group. Group 1 comprised 22 HIV-negative individuals while 38 HIV-positive individuals were classified according to the CDC 1993 classification into group 2 (A1 or A2) or group 3 (B2, A3, B3, C2, C3). All subjects were submitted to upper gastrointestinal endoscopy with duodenal biopsies. Qualitative, semi-quantitative and quantitative histological analyses were performed. Results were considered significant when P < 0.05. A higher prevalence of inflammatory infiltrate and eosinophilia was observed in the HIV group, together with a reduction in mucosal CD4+ lymphocyte (L) counts [median (lower-upper quartiles), 12.82 (8.30-20.33), 6.36 (1.75-11.66) and 1.75 (0.87-3.14) in groups 1, 2 and 3, respectively] which was not correlated with disease stage. The extent of CD4+L count reduction was similar in blood and duodenal mucosa. Normal CD8+L and CD45RO+L counts, and normal numbers of macrophages and antigen-presenting cells were also found in the HIV patients. The cytokine pattern did not differ among groups. Tissue HIV, assessed by p24 antigen, correlated with a higher CD45RO+L count (77.0 (61-79.8) and 43.6 (31.7-62.8) in p24+ and p24-, respectively, P = 0.003), and IL-4 positivity (100 and 48.2 percent in p24+ and p24-, respectively, P = 0.005). The duodenal mucosa of HIV+ patients showed a relatively preserved histological architecture. This finding may be characteristic of a population without opportunistic infections and treated with potent antiretroviral therapy, with a better preservation of the immune status.

Characterization of cellular phenotypes and cytokine expression in balt from children with congenital heart diseases.

UNLABELLED: The present study was performed to target and call attention to the bronchial associated lymphoid tissue (BALT), part of our immune system, from which, we believe, several forms of prophylactic and therapeutic approaches can be developed. The characterization of its immune components, cells, and cytokines, in absence of antigenic stimuli, is pioneer in literature. Eighteen cases of necropsies were chosen and selected the paraffin-embedded lungs. The ages of 11 females and 7 males varied from 5 to 31 months. Cause of death: congenital heart diseases. EXCLUSION CRITERIA: lung infection at necropsy and/or arterial hypertrophy greater than Heath-Edwards' 1st degree. Immunohistochemical technique was applied to identify the cell phenotypes and the cytokines in situ. BALT was identified in all cases in this study. The main cellular phenotypes in BALT were T helper (TH) and B lymphocytes surrounded by T cytotoxic lymphocytes, natural killer cells, and dendritic cells in less quantities. Interleukin 10 and Tumor Necrosis Factor alpha were the predominant cytokines in BALT without antigenic stimuli. BALT is an important structure of the lung immune system in infants, with a tendency to maintain an environment favorable to the Th2 arm of immune response. It needs more exploration to define its behavior in front of infections, especially those with pulmonary tropism.

Lung tissue mechanics in the early stages of induced paracoccidioidomycosis in rats

Pulmonary dysfunction represents the most important cause of death in patients with paracoccidioidomycosis (PBM). In order to investigate the functional changes of the lungs in the early stages of PBM, a model of benign disease was developed by intratracheal challenge of 12-week old isogenic Wistar rats with 1 x 10(6) yeast forms of Paracoccidioides brasiliensis. Animals were studied 30 and 60 days after infection, when fully developed granulomas were demonstrable in the lungs. Measurements of airway reistance, lung elastance and tissue hysteresis were made during sinusoidal deformations (100 breaths/min, tidal volume = 2 ml) with direct measurement of alveolar pressure using the alveolar capsule technique. Infection caused a significant increase in hysteresis (infected: 1.69, N = 13; control: 1.13, N=12,P = 0.024, ANOVA), with no alterations in airway resitance or lung elastance. Histopathological analysis revealed the presence of fully developed granulomas located in the axial compartment of the lung interstitial space. These results suggest that alterations of tissue mechanics represent an early event in experimental PBM.

Comparative and sequential histopathology of plasmodium chabaudi-infected balb/c mice

1. Rodent experimental models have been useful to study severe malaria but few serial and controlled studies have been conducted. In the presente investigation, we describe the histopathology of lethal and non-lethal rodent malaria induced by Plasmodium berghei and P. chabaudi. P. berghei malaria shows a uniformly lethal course, while P. chabaudi malaria produces a non-lethal acute infection with recovery and periodical recurdescences. Sequential histopathological changes were also characterized in P. chabaudi malaria to determine the evolution of the lesions. 2. P. berghei-infected mice have a more severe organ involvement and lower blood regenerative changes than P. chabaudi-infected mice. Two patterns of organ involvement were observed by cimparing the two infections. The first is related to nonspecific parasitized red blood cell clearance by liver and spleen. The second is related to specific changes due to a specific parasite strain interaction with the host, such as those found in the lungs. 3. Sequential changes in P. chabaudi-infected mice were characterized by perihepatocytic reticulin fiber deposition during the recovery from infection, which faded in subsequent stages. Other organs had a similar regressive evolution, except splenic lymphoid tissue which underwent histological restoration or even hypertrophy after depletion in the acute stage. No brain or heart lesions were observed in either model during the acute and subsequent stages. 4. P. chabaudi infection, whose histopathology is described here for the first time, should be useful as a non-lethal experimental model to study the evolution of histological alterations in malaria