RESUMO
Following the emergence of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis-HIV (VL-HIV) coinfections has increased worldwide, mainly in Brazil. The development of clinical forms of VL can be influenced by nutritional status, age, and host genetic factors, which are important variables determining susceptibility to disease. There are no studies with a candidate gene approach assayed directly in the VL-HIV-coinfected population. Herein, we determined and analyzed the associations of SLC11A1, LECT2, CCL1, CCL16, and IL4 genetic polymorphisms with susceptibility to VL-HIV coinfection in Northeastern Brazil. We analyzed 309 DNA samples extracted from the peripheral blood of HIV patients, and clinical and hematological data were collected from medical records. The diagnosis of VL was confirmed in 110 out of 309 patients; genotyping was carried out by TaqMan assays afterwards. Our results confirmed the association between the SLC11A1 polymorphism (rs3731865) and VL-HIV coinfection (p = 0.0206, OR 1.8126, 95% CI 1.1050-2.9727). In addition, the SLC11A1 genotype GG (p = 0.0050, OR 3.0395, 95% CI 1.4065-6.5789) and CD4+ T lymphocyte count (p = 0.0030, OR 0.9980, 95% CI 0.9970-0.9990) were associated with VL-HIV coinfection in a multivariate model. The polymorphism of the SLC11A1 gene (rs3731865) was associated with VL-HIV coinfection, suggesting a possible genetic mechanism involved in the susceptibility to VL in HIV patients. This finding can suggest new therapeutic targets and genetic markers for the VL-HIV-coinfected population.
Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Proteínas de Transporte de Cátions/genética , Predisposição Genética para Doença/genética , Leishmaniose Visceral/epidemiologia , Adulto , Brasil/epidemiologia , Linfócitos T CD4-Positivos/imunologia , Quimiocina CCL1/genética , Quimiocinas CC/genética , Coinfecção/epidemiologia , Coinfecção/genética , Feminino , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interleucina-4/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genéticaRESUMO
BACKGROUND: Falls are common among elderly adults, and are predictors of hospitalization, institutionalization and mortality. OBJECTIVE: The objective of the present study was to examine the relationship between blood-based markers of inflammation and fall events in a sample of elderly Hispanic adults. METHOD: Data were collected from 190 participants enrolled in the Panama Aging Research Initiative study who completed baseline clinical and cognitive assessments. A non-fasting blood sample was obtained. Self-reported falls were classified as no falls, single falls or recurrent (two or more) falls reported in the 12 months prior to baseline evaluations. Serum levels of C Reactive Protein (CRP), T-lymphocyte secreting protein (I-309), interleukin 10 (IL-10), interleukin 6 (IL-6) and interleukin 7 (IL-7) were measured. Global cognition was assessed with the Mini Mental State Examination and depressive symptoms were assessed with the Geriatric Depression Scale (GDS-30). Multinomial logistic regression was used to assess the link between inflammation and fall events. RESULTS: Depressive symptoms, limitations in Instrumental Activities of Daily Living (IADL), IL-7 and I-309 were significantly related to fall events. Elevated levels of IL-7 increased the likelihood of single and recurrent falls, while increased levels of I-309 were associated only with recurrent falls. Greater IADL limitations and depressive symptoms were associated with an increased likelihood of recurrent falls. CONCLUSION: There is a lack of research investigating the relationship between inflammatory biomarkers and fall events. These results provide evidence of risk factors for falls in Hispanic older adults, and could serve to guide public health professionals to establish clinical guidelines to reduce fall risks.
Assuntos
Acidentes por Quedas , Envelhecimento/sangue , Envelhecimento/psicologia , Depressão/sangue , Mediadores da Inflamação/sangue , Acidentes por Quedas/prevenção & controle , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Quimiocina CCL1/sangue , Depressão/complicações , Feminino , Hispânico ou Latino , Humanos , Incidência , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-7/sangue , Masculino , Panamá/epidemiologia , Fatores de RiscoRESUMO
Hybrid vaccines have been investigated in clinical and experimental studies once expresses total antigens of a tumor cell combined with the ability of a dendritic cell (DC) to stimulate immune responses. However, the response triggered by these vaccines is often weak, requiring the use of adjuvants to increase vaccine immunogenicity. Killed Propionibacterium acnes (P. acnes) exerts immunomodulatory effects by increasing the phagocytic and tumoricidal activities of macrophages, promoting DC maturation, inducing pro-inflammatory cytokines production and increasing the humoral response to different antigens. Here, we evaluated the effect of P. acnes on a specific antitumor immune response elicited by a hybrid vaccine in a mouse melanoma model. Hybrid vaccine associated with P. acnes increased the absolute number of memory T cells, the IFN-γ secretion by these cells and the IgG-specific titers to B16F10 antigens, polarizing the immune response to a T helper 1 pattern. Furthermore, the addition of P. acnes to a hybrid vaccine increased the cytotoxic activity of splenocytes toward B16F10 in vitro and avoided late tumor progression in a pulmonary colonization model. These results revealed the adjuvant effect of a killed P. acnes suspension, as it improved specific humoral and cellular immune responses elicited by DC-tumor cell hybrid vaccines.
Assuntos
Adjuvantes Imunológicos , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Imunogenicidade da Vacina , Melanoma Experimental/imunologia , Propionibacterium acnes/imunologia , Animais , Antígenos de Neoplasias/imunologia , Células Cultivadas , Quimiocina CCL1/imunologia , Progressão da Doença , Feminino , Imunoglobulina G/metabolismo , Interferon gama/metabolismo , Linfonodos/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/prevenção & controle , Camundongos Endogâmicos C57BL , Baço/imunologia , Carga Tumoral , Vacinas de Produtos InativadosRESUMO
Rheumatic fever (RF) is an autoimmune disease triggered by Streptococcus pyogenes infection frequently observed in infants from developing countries. Rheumatic heart disease (RHD), the major sequel of RF, leads to chronic inflammation of the myocardium and valvular tissue. T cells are the main population infiltrating cardiac lesions; however, the chemokines that orchestrate their recruitment are not clearly defined. Here, we investigated the expression of chemokines and chemokine receptors in cardiac tissue biopsies obtained from chronic RHD patients. Our results showed that CCL3/MIP1α gene expression was upregulated in myocardium while CCL1/I-309 and CXCL9/Mig were highly expressed in valvular tissue. Auto-reactive T cells that infiltrate valvular lesions presented a memory phenotype (CD4(+)CD45RO(+)) and migrate mainly toward CXCL9/Mig gradient. Collectively, our results show that a diverse milieu of chemokines is expressed in myocardium and valvular tissue lesions and emphasize the role of CXCL9/Mig in mediating T cell recruitment to the site of inflammation in the heart.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Quimiocina CXCL9/metabolismo , Valvas Cardíacas/imunologia , Miocárdio/imunologia , Cardiopatia Reumática/imunologia , Adolescente , Adulto , Movimento Celular/imunologia , Quimiocina CCL1/biossíntese , Quimiocina CCL1/imunologia , Quimiocina CCL3/biossíntese , Quimiocina CCL3/imunologia , Quimiocina CXCL9/biossíntese , Criança , Pré-Escolar , Feminino , Fibrose , Valvas Cardíacas/metabolismo , Humanos , Memória Imunológica/imunologia , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Neovascularização Patológica/imunologia , Febre Reumática/imunologia , Febre Reumática/microbiologia , Streptococcus pyogenes , Adulto JovemRESUMO
A genome-wide scan was conducted for visceral leishmaniasis (VL) in Brazil. Initially, 405 markers were typed in 22 multicase pedigrees (28 nuclear families; 174 individuals; 66 affected). Non-parametric multipoint analysis detected nine chromosomal regions with provisional evidence (logarithm of the odds (LOD) scores 0.95-1.66; 0.003Assuntos
Predisposição Genética para Doença
, Genoma Humano
, Leishmaniose Visceral/genética
, Leishmaniose Visceral/imunologia
, Brasil
, Quimiocina CCL1
, Quimiocinas CC/genética
, Humanos
, Desequilíbrio de Ligação
, Polimorfismo de Nucleotídeo Único
RESUMO
We investigated the role of the platelet activation factor (PAF) receptor (PAFR) in the outcome of infection with Leishmania amazonensis. PAFR deficient (PAFR(-/-)) mice were infected with L. amazonensis and the course of infection was followed. We found that PAFR(-/-) mice in the C57BL/6 background were more susceptible to infection with L. amazonensis than the wild-type controls, as seen both by lesion size and parasite number at the site of infection. Interferon (IFN)-gamma production was delayed in PAFR(-/-) mice, and lower levels of Ccl5 were found in lesions. Expression of nitric oxide synthase-2 mRNA was found impaired in PAFR(-/-) associated with higher levels of arginase-1 mRNA. Moreover, higher levels of antibodies were produced in response to L. amazonensis by PAFR(-/-) mice. We conclude that signaling through the PAFR is essential for the ability of the murine host to control L. amazonensis infection by driving an adequate immune response.
Assuntos
Interferon gama/biossíntese , Leishmania mexicana/imunologia , Leishmaniose Cutânea/imunologia , Glicoproteínas da Membrana de Plaquetas/deficiência , Receptores Acoplados a Proteínas G/deficiência , Animais , Anticorpos Antiprotozoários/sangue , Arginase/biossíntese , Quimiocina CCL1 , Quimiocina CCL5 , Quimiocinas CC/análise , Modelos Animais de Doenças , Suscetibilidade a Doenças , Expressão Gênica , Histocitoquímica , Imunoglobulina G/sangue , Interleucina-10/análise , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/biossíntese , Glicoproteínas da Membrana de Plaquetas/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Receptores Acoplados a Proteínas G/genética , Fator de Necrose Tumoral alfa/análise , Regulação para CimaRESUMO
CC chemokine ligand (CCL)1/I-309 is a potent attractant for T-helper cell type 2 lymphocytes. The present study investigates whether this cytokine is released in the bronchoalveolar fluid (BALF) of asthmatic patients. Measurements of CCL1 using ELISA showed that levels of this cytokine were significantly elevated in BALF from asthmatics compared with normals (median (range) 193 (120-449) pg.mL(-1) versus 30 (21-55) pg.mL(-1)). Differential cell counts in BALF showed that either lymphocyte or eosinophil numbers were elevated in asthmatic compared with normal subjects (10.8 x 10(3).mL(-1) versus 1.0 x 10(3).mL(-1) and 1.7 x 10(3).mL(-1) versus 0.2 x 10(3).mL(-1), respectively). There was a trend towards a significant correlation between CCL1 levels and lymphocyte numbers in BALF. Separation of BALF using sequential CCL1 affinity column and reverse-phase high-performance liquid chromatography allowed detection of biologically active CCL1. Using immunohistochemistry, CCL1 immunoreactivity was localised predominantly to the airway epithelium. Interestingly, there was a significant correlation between CC chemokine ligand 1 levels and epithelial cell numbers in bronchoalveolar lavage fluid and between these cells and lymphocyte numbers. Moreover, interleukin-4, interleukin-13 and interferon-gamma stimulated primary bronchial airway epithelial cells to release CC chemokine ligand 1. These findings suggest that CC chemokine ligand 1 may play a role in lymphocyte recruitment in bronchial asthma.