Cerebral complement C1q activation in chronic Toxoplasma infection.

Exposure to the neurotropic parasite, Toxoplasma gondii, causes significant brain and behavioral anomalies in humans and other mammals. Understanding the cellular mechanisms of T. gondii-generated brain pathologies would aid the advancement of novel strategies to reduce disease. Complement factor C1q is part of a classic immune pathway that functions peripherally to tag and remove infectious agents and cellular debris from circulation. In the developing and adult brain, C1q modifies neuronal architecture through synapse marking and pruning. T. gondii exposure and complement activation have both been implicated in the development of complex brain disorders such as schizophrenia. Thus, it seems logical that mechanistically, the physiological pathways associated with these two factors are connected. We employed a rodent model of chronic infection to investigate the extent to which cyst presence in the brain triggers activation of cerebral C1q. Compared to uninfected mice, cortical C1q was highly expressed at both the RNA and protein levels in infected animals bearing a high cyst burden. In these mice, C1q protein localized to cytoplasm, adjacent to GFAP-labeled astrocytes, near degenerating cysts, and in punctate patterns along processes. In summary, our results demonstrated an upregulation of cerebral C1q in response to latent T. gondii infection. Our data preliminarily suggest that this complement activity may aid in the clearance of this parasite from the CNS and in so doing, have consequences for the connectivity of neighboring cells and synapses.

Chitinase dependent control of protozoan cyst burden in the brain.

Chronic infections represent a continuous battle between the host's immune system and pathogen replication. Many protozoan parasites have evolved a cyst lifecycle stage that provides it with increased protection from environmental degradation as well as endogenous host mechanisms of attack. In the case of Toxoplasma gondii, these cysts are predominantly found in the immune protected brain making clearance of the parasite more difficult and resulting in a lifelong infection. Currently, little is known about the nature of the immune response stimulated by the presence of these cysts or how they are able to propagate. Here we establish a novel chitinase-dependent mechanism of cyst control in the infected brain. Despite a dominant Th1 immune response during Toxoplasma infection there exists a population of alternatively activated macrophages (AAMØ) in the infected CNS. These cells are capable of cyst lysis via the production of AMCase as revealed by live imaging, and this chitinase is necessary for protective immunity within the CNS. These data demonstrate chitinase activity in the brain in response to a protozoan pathogen and provide a novel mechanism to facilitate cyst clearance during chronic infections.

Lack of inflammation or immune response in cyst tissue of patients with symptomatic non-hydrocephalic pineal cysts.

Pineal cysts are frequently encountered as incidental findings in magnetic resonance imaging, usually devoid of symptoms, yet some patients exhibit symptomatic manifestations possibly associated with the cyst, even in the absence of hydrocephalus. The etiology of these symptoms remains contentious. This study aims to investigate the presence of lymphatic endothelial cell (LEC) markers and indications of inflammation or immune response within the pineal cysts of patients experiencing symptomatic non-hydrocephalic presentations. Eight patients who underwent surgical excision of their cysts were included in the study. Immunohistochemistry was utilized to assess the expression of LYVE-1, PDPN, and VEGFR3 as LEC markers, alongside IL-6 and CD3 for indications of inflammation or immune activity. Our analysis revealed an absence of inflammatory markers or immune response. However, a distinct expression of VEGFR3 was observed, likely localized to neurons within the pineal cyst tissue. We propose that these VEGFR3+ neurons within the pineal cyst may contribute to the headache symptoms reported by these patients. Further investigations are warranted to substantiate this hypothesis.

Cystic lymphoid hyperplasia: an orofacial lesion strongly associated with HIV and AIDS.

AIMS: Cystic lymphoid hyperplasia (CLH) frequently affects the parotid gland in human immunodeficiency virus (HIV)-infected patients. This clinicopathological study, comprising 167 cases, aims to define the clinical-pathological parameters of CLH in order to elucidate the aetiopathogenesis. METHODS AND RESULTS: This retrospective study of 167 archival cases of CLH recorded patients' age, race and gender, and the nature, site and symptoms of CLH. A total of 109 cases were reviewed histologically and analyzed for HIV-1 p24 antigen immunopositivity using standard procedures. CLH of the parotid gland showed a male predominance, whereas submandibular gland (P = 0.27) and bilateral parotid involvement favoured females (2:1). CLH occurred at a younger mean age in females than males in the parotid gland (P = 0.0035) and in the submandibular gland (P = 0.0032). Intra-lymph nodal origin was favoured, with 76.1% of cases occurring within entrapped salivary gland remnants. P24 staining revealed ~90% sensitivity in HIV-associated CLH. CONCLUSION: CLH should be used preferentially to describe parotid enlargement in HIV-infected patients. This study strongly supports the hypothesis that CLH develops following ductal ectasia of entrapped salivary gland inclusions arising within lymph nodes. CLH should be classified as an orofacial lesion associated strongly with HIV and AIDS.

Mechanisms regulating monocyte CXCL8 secretion in neurocysticercosis and the effect of antiparasitic therapy.

Neurocysticercosis (NCC) due to infection with Taenia solium is a major cause of epilepsy worldwide. Larval degeneration, which may follow antiparasitic treatment, results in clinical symptoms due to inflammatory cell influx. Mechanisms regulating this are not well understood, but chemokines have a key role. Stimulation of human monocytes by cyst Ags from NCC-infected pigs showed that scolex and membrane Ags drive CXCL8 and CCL2 secretion. Antiparasitic treatment of pigs increased CXCL8 in response to brain, but not muscle, cyst Ags. Cyst-fluid Ags did not elicit monocyte chemokine secretion, inhibited LPS-induced CXCL8 by up to 89%, but did not alter CCL2 secretion. This effect was inhibited by anti-IL-10 Abs. Plasma CXCL8, TNF-α, IL-10, eotaxin, IL-1, IL-1ra, soluble IL-1R-II, and soluble TNFR-I and -II levels were evaluated in 167 NCC patients. Patients had lower plasma CXCL8 and TNF-α concentrations than control subjects. In summary, larval Ags from brain and muscle cysts differentially regulate chemokine secretion. Cyst-fluid inhibits CXCL8, and this is blocked by anti-IL-10 Abs. CXCL8 concentrations are decreased in patient plasma. Following anti-parasitic therapy, scolex and membrane Ags are exposed, and cyst fluid is decreased, leading to inflammatory cell influx. Taken together, the cellular, porcine, and human data may explain, in part, why NCC is usually asymptomatic but may cause proinflammatory symptoms, particularly following treatment.

Isolated splenic peliosis in an immunocompromised patient.

BACKGROUND: Peliosis is a rare condition characterised by multiple cyst-like, blood-filled cavities within the parenchyma of solid organs, most commonly affecting the liver. Isolated splenic peliosis is an even more unusual phenomenon. Patients with AIDS may develop peliosis in association with bacillary angiomatosis. This is due to secondary infection with Bartonella henselae or a similar organism, Rochalimaea henselae. CASE PRESENTATION: A 45-year-old HIV-positive man on antiretroviral therapy presented with a left hypochodrial abdominal mass. Radiological and histopathological examination confirmed splenic peliosis.

Cystic pulmonary tuberculoma.

Pulmonary tuberculosis (TB) is a medical and social problem, particularly in developing countries. Early diagnosis and treatment is important. Chest radiography is usually the first diagnostic tool when there is a suspicion of pulmonary TB. A computed tomography (CT) scan provides more accurate information on the extent and distribution of pulmonary TB. We present here a young, immunocompetent male patient with unusual imaging findings for pulmonary TB. We discuss the clinical presentation and management.

Accuracy of an experimental whole-blood test for detecting reactivation of echinococcal cysts.

BACKGROUND: Cystic echinococcosis (CE) is a complex disease for which clear understanding of clinical manifestations is needed to avoid misdiagnosis, inappropriate treatment, and severe complications. We evaluated the accuracy of a whole-blood stimulation test based on Interleukin (IL)-4 detection in response to Antigen B (AgB) of Echinococcus granulosus sensu lato to discriminate cyst viability and detect cyst reactivation in patients with hepatic CE. METHODOLOGY/PRINCIPAL FINDINGS: Thirty patients with CE3b cysts and 37 patients with spontaneously-inactivated CE4-CE5 cysts were recruited (T0). After enrollment, 5 patients with CE3b cysts received albendazole, resulting in cyst solidification (CE4) in 4/5. Within a two-year follow-up, the whole-blood test was repeated at two time-points, in ≥14 (T1) and in ≥4 (T2) patients per group. IL-4 and a panel of other soluble factors were measured in the stimulated plasma. Baseline IL-4 levels were significantly higher in patients with CE3b compared to those with CE4 cysts (p = 0.006). Test accuracy for CE3b diagnosis had a sensitivity of 33-60% and a specificity of 76-95%, depending on the cut-off applied. Overall, IL-4 levels did not change significantly over time in either group; however, patients within the CE3b group showed a significant decrease of IL-1ra, IL-6, IL-8, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, FGF at T1 compared to T0 (p≤0.042). CONCLUSIONS/SIGNIFICANCE: Whole-blood IL-4-response to AgB is significantly higher in patients with active compared to inactive CE but apparently not modulated over time after treatment. On the contrary, the levels of IL-1ra, IL-6, IL-8, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, FGF significantly decreased in active CE during follow-up. Additional studies are needed to understand whether these findings might have a clinical significance for patients' follow-up.

Localization of a molecule immunochemically similar to eosinophil major basic protein in human placenta.

We have recently reported that human pregnancy is characterized by a 10- to 20-fold elevation of eosinophil major basic protein (MBP) immunoreactivity in maternal blood. Here we show, by immunofluorescence, that placental tissue specifically binds antibody to MBP in and around the placental X cells and placental-site giant cells and, using thin plastic sections, that placenta has no infiltrating eosinophils. The X cells line the inner aspects of placental septal cysts, and the cyst fluid, obtained by aspiration, contains immunoreactive MBP at concentrations of 100 micrograms/ml, a sixfold greater concentration than the highest levels measured in maternal blood. The soluble MBP immunoreactivities in placental homogenates and in maternal serum chromatograph identically on Sephadex G-50, and both these gestational MBP molecules migrate as though substantially larger than the MBP found in serum from patients with hypereosinophilic syndrome or purified from the eosinophil granule. Our inability to demonstrate eosinophils in maternal blood or placental tissue, coupled with the large quantities of immunoreactive MBP highly localized in placental cysts and the chromatographic behavior of this molecule, suggest that the MBP detected in human gestation is produced by placenta.

Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor.

We have recently described a new form of light chain deposition disease (LCDD) presenting as a severe cystic lung disorder requiring lung transplantation. There was no bone marrow plasma cell proliferation. Because of the absence of disease recurrence after bilateral lung transplantation and of serum-free light chain ratio normalization after the procedure, we hypothesized that monoclonal light chain synthesis occurred within the lung. The aim of this study was to look for the monoclonal B-cell component in 3 patients with cystic lung LCDD. Histologic examination of the explanted lungs showed diffuse nonamyloid kappa light chain deposits associated with a mild lymphoid infiltrate composed of aggregates of small CD20(+), CD5(-), CD10(-) B lymphocytes reminiscent of bronchus-associated lymphoid tissue. Using polymerase chain reaction (PCR), we identified a dominant B-cell clone in the lung in the 3 studied patients. The clonal expansion of each patient shared an unmutated antigen receptor variable region sequence characterized by the use of IGHV4-34 and IGKV1 subgroups with heavy and light chain CDR3 sequences of more than 80% amino acid identity, a feature evocative of an antigen-driven process. Combined with clinical and biologic data, our results strongly argue for a new antigen-driven primary pulmonary lymphoproliferative disorder.

Expression of cytokines IL-1beta and TNF-alpha in tissues and cysts surrounding Didymocystis wedli (Digenea, Didymozoidae) in the Pacific bluefin tuna (Thunnus orientalis).

Tuna long distance migrations and exposure to wide range of ambient water temperatures facilitate infections with several parasitic groups. This is reflected in the remarkable diversity of tuna parasite communities, especially members of Didymozoidae superfamily (Poche, 1907) (Trematoda, Digenea). Didymocystis wedli is the most frequent species encountered in bluefin tuna parasitizing gill filaments, therefore suggested as a biological marker to differentiate between discrete tuna Atlantic stocks. Because of its high occurrence in gill tissue and inflammatory reaction as the consequence, the aim of our study was to asses if inflammatory madiation through expression of IL-1beta and TNF-alpha is present locally at the site of D. wedli encystment, as well as if the systematic expression of cytokines can be detected in different tissues of infected versus uninfected fish. Quantification of localized cytokine expression was done on paraffine embedded gill sections by in situ hybridization, while quantitative PCR was used to mesured cytokine transcripts in skin mucus, kidney, spleen, gills and liver. Our results suggest that tuna constitutive expression of IL-1beta and TNF-alpha in gills and skin implies a well-adapted innate immunity present at the barrier between the organism and environment. Upregulation of both cytokines in Didymocystis-infected gills not followed by a systematic response evidences the ongoing of an inflammatory process specific for the parasitation site. However, the lack of intensive cytokines response to D. wedli observed by molecular and histological data that fails to eliminate the parasite, could be related to the "old" age of the parasitic process.

Radiological features of Pneumocystis jirovecii Pneumonia in immunocompromised patients with and without AIDS.

The aim of this study was to compare chest computerized tomography (CT) findings of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without acquired immune deficiency syndrome (AIDS). Chest CT findings and clinical parameters of 38 consecutive immunocompromised patients, nine with AIDS and 29 with other causes of immunosuppression, were characterized and compared. PCP in patients without AIDS was diagnosed after a significantly shorter time interval from symptom onset: 8 +/- 6 vs. 18 +/- 1.0 days (p = 0.024). From a radiographic point of view, non-AIDS patients had a significantly higher proportion of diffuse ground glass lesions, 86 vs. 44% (p = 0.02), and a lower proportion of cystic lesions, 3 vs. 56% (p = 0.015). The two subgroups did not differ in smoking status and the number of pack-years. On multivariant analysis, only the presence of AIDS was found to be a risk factor for the formation of pulmonary cystic lesions. Different immune reactions to the parasite P. jirovecii in immunocompromised patients with and without AIDS results in a different time lag between symptoms and a correspondingly different radiographic pattern: widespread ground glass opacities in the former and cystic lesions in the latter.

The role of inflammation in the genesis of the cystic component of craniopharyngiomas.

BACKGROUND: Craniopharyngioma accounts for 5-10% of childhood tumors and, despite of the benign histological features, its clinical course can be malignant because of critical anatomical relationships with neural and vascular structures and the possible morbidity associated to resection. Only a few studies have addressed the molecular characterization of the cyst fluid so far and the mechanisms of action of intracystic agents are not clearly understood yet. METHODS: The acidic soluble proteins contained in the cystic fluid of six patients with cystic craniopharyngioma, three of them treated with intratumoral interferon-α, were analyzed. A high performance liquid chromatography electrospray ionization mass spectrometry analysis was performed. FINDINGS: The antimicrobial peptides α-defensins 1-3 relevant for innate immunity were detected in the cystic fluid before the intratumoral treatment. Amount of peptides significantly decreased in cystic fluid during pharmacological treatment. INTERPRETATION: Detection of α-defensins 1-3 excludes that cyst fluid formation can derive from disruption of blood-brain barrier and suggests the involvement of innate immune response in pathology of craniopharyngioma cyst formation. The reduction of α-defensins could derive both from direct antitumoral effect of interferon-α on squamous epithelial cells of craniopharyngioma cyst and from its immuno-modulatory effects on the recruitment of cells of innate immune systems. Interestingly, the clinical patient outcome well correlates with the gradual reduction of α-defensins 1-3 amount. Additional studies will be necessary to establish the role of these molecules in the pathogenesis of craniopharyngioma, and further investigations will be necessary to confirm the efficacy of the antitumoral activity of interferon-α.

Anti-thyroid peroxidase antibody and subclinical hypothyroidism in relation to hypertension and thyroid cysts.

Hypertension frequently occurs in subclinical hypothyroidism (SCH). By bolstering thyroid inflammation, anti-peroxidase antibody (TPO-Ab) causes autoimmune thyroiditis, which is one of the most common causes of SCH. Since the absence of thyroid cysts is associated with TPO-Ab (+) based on the indication of latent thyroid damage, we explored the potential mechanism underlying the association among TPO-Ab, SCH, hypertension, and thyroid cysts. A cross-sectional study of 1,483 Japanese aged 40-74 years was conducted. Thyroid cysts were defined as those having a maximum diameter of ≥ 2.0 mm, containing no solid component. TPO-Ab (+) was positively associated with SCH with hypertension (adjusted odds ratio [OR] and 95% confidence interval [CI], 2.62 [1.40, 4.89]) but not with SCH without hypertension (0.84 [0.37, 1.89]), respectively. Moreover, among participants without thyroid cysts, SCH was positively associated with hypertension (2.15 [1.23, 3.76]) but not among participants with thyroid cysts (0.58 [0.16, 2.16]), respectively. TPO-Ab was positively associated with SCH with hypertension, but not with SCH without hypertension. In addition, status of thyroid cysts might act as a determinant factor on the association between SCH and hypertension. These findings are efficient tools to clarify the background mechanism that underlies SCH.

Multiplex cytokine and antibody profile in cystic echinococcosis patients during a three-year follow-up in reference to the cyst stages.

BACKGROUND: Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by infection of the larval stage of tapeworm Echinococcus granulosus. In human CE, the parasites develop and form cysts in internal organs. The differentiated cysts can be classified into five types based on WHO-IWGE standard CE1-5 representing different developmental stages. Infection with E. granulosus triggers hosts' humoral and cellular response, displaying elevated serum antibodies and Th1 and Th2 cytokines, which are presumed to be in association with the disease outcome. Identification of immunological markers for evaluation of disease progression has been a growing concern. However, the distinctive profile of cytokines and antibodies associated with the cyst progression has not been ascertained. METHODS: To better understand the interaction between host immune response and disease outcome, the present study followed-up four CE patients over three years by yearly measuring serum level of 27 cytokines, total IgG and isotypes, and ultrasound scanning, beginning in year 1 for all patients with CE1 and CE2 cysts before treatment and continued in year 2 with CE4 and in year 3 with CE3-CE5 post-treatment. RESULTS: Nine cytokines including Th1-type IL-2, Th17-type IL-17A, and inflammatory cytokines IL-1ß, IL-1Rα and TNF-α, chemokines IL-8, MIP-1α, MIP-1ß, and growth factor G-CSF were significantly elevated in patients with cyst type CE1, compared to the normal controls, and then declined to a normal level at CE4 and CE5. Examining the antibody production, we found that serum specific IgG was significantly increased in patients with active and transitional cysts, specifically the total IgG at CE1/CE3/CE4-CE5, IgG4 at CE1 and IgG1 at CE1/CE3 cyst status, in comparison with the normal controls, but showed no significant changes between the cyst stages. CONCLUSIONS: Our findings provide new information on the profile of multiplex cytokines and serum antibodies associated with cyst stages in cystic echinococcosis patients through a three-year follow-up, implying that further studies using an approach combining cyst-associated immune parameters may aid in identifying immunological markers for differentiation of disease progression.

A Rare Case of Extensive Unilateral Ureteritis Cystica.

Ureteritis cystica is rare, benign entity that associates with chronic urothelial irritation such as recurrent urinary tract infection or nephrolithiasis. It is often diagnosed incidentally on routine imaging or ureteroscopy in asymptomatic individuals. In this case report, we present the retrograde pyelogram and ureteroscopy images of a rare case of extensive unilateral ureteritis cystica in a 78-year-old female presenting for elective stone surgery.

The association of host age and gender with inflammation around neurocysticercosis cysts.

The results of previous investigations indicate that age and gender may influence the strength of the human host's immune response to infection of the central nervous system with the larvae of Taenia solium. Most of the relevant research on such neurocysticercosis (NCC) has, however, been conducted on hospital-based samples in developing countries, where differential access to healthcare may bias the study results. Using data from 171 NCC patients participating in a treatment trial, the associations of patient age and gender with the presence of inflammation around NCC cysts (i.e. cysts in the transitional phase) have recently been explored, after controlling for measures of economic and geographical access to healthcare. Data on cysts were collected from computed-tomography or magnetic-resonance images taken at four time-points, from baseline to 12-months post-treatment. The odds of having transitional cysts were evaluated by logistic regression whereas Poisson regression was used to explore the numbers of transitional cysts, with generalised estimating equations (GEE) used to account for the multiple observations over time. After controlling for healthcare access, the odds of having transitional cysts were found to be 1.5-fold higher for the female patients than for the male, although this association was not statistically significant (P = 0.136). In the Poisson model, however, the number of transitional cysts was found to be 1.8-fold higher in the female patients than in the male, and this gender effect was not only statistically significant (P = 0.002) but also constant over time. The association of host age with transitional cysts was more complicated, with significant interaction between age and time. It therefore appears that there are significant gender and age differences in the local immune response to NCC, even after adjusting for differences in healthcare access.

Ciliated hepatic foregut cyst discovered after kidney transplantation in a hepatitis C virus-infected patient: a report of one case and review of the literature.

Ciliated hepatic foregut cyst (CHFC) is a rare liver lesion derived from the embryonic foregut. In most cases, CHFC remains asymptomatic but some malignant transformations have been reported. Typical imaging features usually lead to diagnosis using ultrasonography, computed tomography scan examination or MRI. When the diagnosis remains uncertain, a fine needle aspiration with cytology is appropriate. The presence of ciliated epithelial cells with hepatocytes and mucous cells on aspiration cytology is enough to assess the diagnosis. Surgery is recommended when there is uncertain diagnosis or malignant lesion suspicion. We report herein, the case of a CHFC discovered in a hepatitis C virus-infected patient following a renal transplantation. To eliminate a lymphoma or a liver tumor arising because of patient's immunosuppression status, a surgical resection of the lesion was performed. The surgical outcome was uneventful. Regarding this case, embryogenesis, morphological characteristics and treatment of the lesions are discussed.

[A method for the combined treatment of chronic cystic sinusitis].

A pathogenetically substantiated method is proposed for the combined treatment of chronic cystic sinusitis that includes sparing surgical intervention and postoperative treatment with ximedone, a regenerator drug with immunotropic activity.