Inducible Nitric Oxide Synthase in Heart Tissue and Nitric Oxide in Serum of Trypanosoma cruzi-Infected Rhesus Monkeys: Association with Heart Injury

Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi, afflicts from 8 to 15 million people in the Latin America. Chronic chagasic cardiomyopathy (CCC) is the most frequent manifestation of Chagas disease. Currently, patient management only mitigates CCC symptoms. The pathogenic factors leading to CCC remain unknown; therefore their comprehension may contribute to develop more efficient therapies. In patients, high nitric oxide (NO) levels have been associated with CCC severity. In T. cruzi-infected mice, NO, mainly produced via inducible nitric oxide synthase (iNOS/NOS2), is proposed to work in parasite control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, infected rhesus monkeys and iNOS/NOS2-deficient mice were used to explore the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. Chronically infected monkeys presented electrical abnormalities, myocarditis and fibrosis, resembling the spectrum of human CCC. Moreover, cardiomyocyte lesion correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue. Our findings support that parasite-driven iNOS/NOS2+ cells accumulation in the cardiac tissue and NO overproduction contribute to cardiomyopathy severity, mainly disturbing the pathway involved in electrical synchrony in T. cruzi infection

Phenotypes of lung mononuclear phagocytes in HIV seronegative tuberculosis patients: evidence for new recruitment and cell activation

Mycobacterium tuberculosis preferentially resides in mononuclear phagocytes. The mechanisms by which mononuclear phagocytes keep M. tuberculosis in check or by which the microbe evades control to cause disease remain poorly understood. As an initial effort to delineate these mechanisms, we examined by immunostaining the phenotype of mononuclear phagocytes obtained from lungs of patients with active tuberculosis. From August 1994 to March 1995, consecutive patients who had an abnormal chest X-ray, no demostrable acid-fast bacilli in sputum specimens and required a diagnostic bronchoalveolar lavage (BAL) were enrolled. Of the 39 patients enrolled, 21 had microbiologically diagnosed tuberculosis. Thirteen of the 21 tuberculosis patients were either HIV seronegative (n = 12) or had no risk factor for HIV and constituted the tuberculosis group. For comparison, M. tuberculosis negative patients who had BAL samples taken during this time (n = 9) or normal healthy volunteers (n = 3) served as control group. Compared to the control group, the tuberculosis group had significantly higher proportion of cells expressing markers of young monocytes (UCHM1) and RFD7, a marker for phagocytic cells, and increased expression of HLA-DR, a marker of cell activation. In addition, tuberculosis group had significantly higher proportion of cells expressing dendritic cell marker (RFD1) and epithelioid cell marker (RFD9). These data suggest that despite recruitment of monocytes probably from the peripheral blood and local cell activation, host defense of the resident lung cells is insufficient to control M. tuberculosis

Retinochoroiditis toxoplasmosis susceptibility and gene polymorphism

Submitted by Sandra Infurna ([email protected]) on 2017-05-18T11:11:38Z No. of bitstreams: 1 maira2_albuquerque_etal_IOC_2012.pdf: 74108 bytes, checksum: e6472747ac322f9c725d45d7d49e056c (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-05-18T11:18:08Z (GMT) No. of bitstreams: 1 maira2_albuquerque_etal_IOC_2012.pdf: 74108 bytes, checksum: e6472747ac322f9c725d45d7d49e056c (MD5)Made available in DSpace on 2017-05-18T11:18:09Z (GMT). No. of bitstreams: 1 maira2_albuquerque_etal_IOC_2012.pdf: 74108 bytes, checksum: e6472747ac322f9c725d45d7d49e056c (MD5) Previous issue date: 2012Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxoplasmose. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Imunologia e Imonogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxoplasmose. Rio de Janeiro, RJ. Brasil

TNFR1 single nucleotide polymorphisms are not associated with cervical HPV-induced pre-malignant lesion but regulate in situ cervical TNFR1 expression

Submitted by Janaína Nascimento ([email protected]) on 2019-03-19T14:24:44Z No. of bitstreams: 1 ve_Rocha_Natália_etal_INI_2019.pdf: 3415620 bytes, checksum: dcec2b0d13083210cf995db8672638bd (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-03-22T19:36:22Z (GMT) No. of bitstreams: 1 ve_Rocha_Natália_etal_INI_2019.pdf: 3415620 bytes, checksum: dcec2b0d13083210cf995db8672638bd (MD5)Made available in DSpace on 2019-03-22T19:36:22Z (GMT). No. of bitstreams: 1 ve_Rocha_Natália_etal_INI_2019.pdf: 3415620 bytes, checksum: dcec2b0d13083210cf995db8672638bd (MD5) Previous issue date: 2019Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Laboratório de Anatomia Patológica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.State University of Rio de Janeiro. Department of Biochemistry. Rio de Janeiro, RJ, Brazil.State University of Rio de Janeiro. Department of Rheumatology. Rio de Janeiro, RJ, Brazil.State University of Rio de Janeiro. Department of Biochemistry. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.TNF-α is involved in HPV infection control by triggering cell signaling through binding in specific receptors TNFR1 and TNFR2. Genetic polymorphisms in these receptors may influence TNF-α signaling. Herein, we investigated TNFR1 rs767455 andrs2234649 single nucleotide polymorphisms, and TNFR1 protein expression in cervical squamous intraepithelial lesions (SIL) to identify their role in cervical pre-malignant development. SIL patients (n = 179) and healthy volunteers (n = 227) were enrolled for TNFR1 genotyping analysis by PCR-RFLP in blood samples and TNFR1 protein expression in cervical tissue by immunohistochemistry. No statistical differences regard genotypes and allelic frequencies for both polymorphisms were observed. Cervical TNFR1-expressing cells were rare in epithelium and basal layer regardless the groups. However, a progressive increase in infiltrating cells was observed in the stromal area, mainly in high SIL (HSIL) group compared to low SIL (LSIL, p <0.001) and control (p < 0.001) groups. TNFR1-expressing cells frequency was higher in TNFR1 rs767455AG/GG (p < 0.001), and in rs2234649AA (p < 0.001) genotypes carries in HSIL subgroup. These data indicated that TNFR1-expression is abrogated in cervical epithelium, where HPV-induced pre-malignant lesion occurs, increasing its frequency in inflammatory cells in stroma, and is genetically controlled by TNFR1 rs767455AG/GG and rs234649AA genotypes. These biomarkers may be useful to identify cervical precancerous lesions progression

Cardiomyocyte injury in <i>T. cruzi</i>-infected rhesus monkeys.

<p>Cardiomyocyte damage was assessed by immunohistochemical detection of Cx43 in the myocardium of the left ventricle and CK-MB activity levels in the serum of noninfected and chronically <i>T. cruzi</i>-infected rhesus monkeys. (<b>A</b>) Photomicrograph of myocardium section of the left ventricle of the noninfected monkey #94 showing normal pattern of Cx43 expression in intercalated discs. (<b>B</b>) Photomicrograph of myocardium section of the left ventricle of the <i>T. cruzi</i>-infected monkey #64 (23 ypi) showing normal aspect. (<b>C</b>) Photomicrograph of left ventricle section of the <i>T. cruzi</i>-infected monkey #99 (20 ypi) showing normal Cx43 pattern. (<b>D</b>) Photomicrograph of section of left ventricle of the <i>T. cruzi</i>-infected monkey #90 (20 ypi) revealing Cx43 loss in myocardial area lacking inflammation. (<b>E–F</b>). Photomicrographs of left ventricle section of the cardiopatic <i>T. cruzi</i>-infected monkey #95 (20 ypi) showing Cx43 loss in area with (<b>E</b>) intense diffuse inflammation and (<b>F</b>) the substitution of cardiomyocytes by mesenchymal cells. (<b>G</b>) Frequency of stained Cx43 area in heart sections of noninfected and chronically <i>T. cruzi</i>-infected monkeys (20–23 ypi). (<b>H</b>) Detection of CK-MB activity in the serum of noninfected and chronically <i>T. cruzi</i>-infected monkeys (20–23 ypi). (<b>I</b>) Correlation between the number of iNOS/NOS2⁺ cells in heart tissue and CK-MB activity levels in serum of rhesus monkeys. Bar = 100 µm.</p

Increased collagen deposits in the myocardium of <i>T. cruzi</i>-infected rhesus monkeys.

<p>Collagen deposition was used to assess fibrosis in the myocardium of the left ventricle of noninfected and <i>T. cruzi</i>-infected monkeys. (<b>A</b>) Noninfected monkey #94, normal slight collagen deposits. (<b>B</b>) Monkey #67 (41 dpi), increased collagen deposition. (<b>C</b>) Monkey #45 (3 ypi), normal collagen deposits. (<b>D</b>) Monkey #64 (23 ypi), increased collagen deposition. (<b>E</b>) Monkey #99 (20 ypi) normal slight collagen deposits. (<b>F</b>) Monkey #95 (20 ypi), increased interstitial matrix deposits. <b>G.</b> Percentage of cardiac section area occupied by collagen deposits in the myocardium of the left ventricle of noninfected and <i>T. cruzi</i>-infected monkeys. (<b>H–K)</b> Serial heart sections of monkey #95 (20 ypi) showing: (<b>H</b>) intense infiltrates of mononuclear inflammatory cells (<b>I</b>) paralleling fibrosis, and (<b>J</b>) substitution of cardiomyocytes by mesenchymal cells in (<b>K</b>) an area of intense fibrosis. <b>A–F</b>, <b>I</b> and <b>K</b>, Picro-Sirius red stain. <b>H</b> and <b>J</b>, H&E. Bar = 100 µm.</p