RESUMO
COVID-19 is caused by SARS-CoV-2 infection and leads from asymptomatic to severe outcomes. The recurrence of the COVID-19 has been described, however, mechanisms involved remains unclear. Thus, the work aimed to investigate the role of multifunctional T cells in patients with recurrent COVID-19. We evaluated clinical characteristics, presence of anti-S1 and anti-Nucleocapsid IgG in patients' sera, and multifunctional T cells (for IFN-γ, IL-2, and TNF-α) in patients with multiple episodes of COVID-19 and controls. Data demonstrate that patients with recurrent COVID-19 have a T cell pattern predominantly related to IFN-γ production. Also, patients with COVID-19 history and absence of anti-S1 IgG had lower levels of CD4+ IFN + IL-2 + TNF + T cells independently of number of disease episodes. Complementary, vaccination changed the patterns of T cells phenotypes and induced IgG seroconversion, despite not induce higher levels of multifunctional T cells in all patients. In conclusion, the data suggest that recurrent disease is related to early-disease T cell profile and absence of anti-S1 IgG is related to lower multifunctional CD4 T cell response, what suggests possibility of new episodes of COVID-19 in these patients.
Assuntos
COVID-19 , Interleucina-2 , Humanos , SARS-CoV-2 , Linfócitos T CD4-Positivos , Imunoglobulina GRESUMO
PURPOSE: Several interactions exist between the GH/IGF axis and the immune system, including effects on innate immunity and humoral and cellular response. Acquired GH deficiency (GHD) has been recently proposed as a risk factor for severity of COVID-19 infections. However, acquired GHD is often associated to other factors, including pituitary tumors, surgery, radiotherapy, and additional pituitary hormones deficits and their replacements, which, together, may hinder an accurate analysis of the relationship between GHD and COVID-19. Therefore, we decided to assess the seroprevalence of SARS-CoV-2 antibodies and the frequency of symptomatic cases of COVID-19 in adults subjects with untreated isolated GHD (IGHD) due to a homozygous null mutation in the GHRH receptor gene. METHODS: A cross-sectional study was carried out in 27 adult IGHD subjects and 27 age- and gender-matched local controls. Interview, physical examination, bio-impedance, hematological and SARS-CoV-2 IgM and IgG antibodies were analyzed. RESULTS: There was no difference in the prevalence of positivity of anti-SARS-CoV-2 IgM and IgG antibodies between the two groups. Conversely, no IGHD individual had a previous clinical diagnosis of COVID-19 infection, while 6 control subjects did (p = 0.023). CONCLUSION: The production of anti-SARS-CoV-2 antibodies was similar between IGHD subjects due to a GHRH receptor gene mutation and controls, but the evolution to symptomatic stages of the infection and the frequency of confirmed cases was lower in IGHD subjects than in GH sufficient individuals.
Assuntos
COVID-19 , Hormônio do Crescimento Humano , Adulto , Estudos Transversais , Humanos , Mutação , Receptores de Neuropeptídeos , Receptores de Hormônios Reguladores de Hormônio Hipofisário , SARS-CoV-2 , Estudos SoroepidemiológicosRESUMO
Through whole-genome sequencing analysis, we identified non-Leishmania parasites isolated from a man with a fatal visceral leishmaniasis-like illness in Brazil. The parasites infected mice and reproduced the patient's clinical manifestations. Molecular epidemiologic studies are needed to ascertain whether a new infectious disease is emerging that can be confused with leishmaniasis.
Assuntos
Infecções por Euglenozoa/epidemiologia , Infecções por Euglenozoa/parasitologia , Trypanosomatina/genética , Idoso , Animais , Brasil/epidemiologia , DNA Espaçador Ribossômico , Genes de Helmintos , Humanos , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Masculino , Camundongos , Filogenia , Trypanosomatina/classificaçãoRESUMO
Congenital Zika syndrome (CZS) is a cluster of malformation, and the mechanisms that lead it are still unclear. Using hypothesis-driven candidate genes and their function in viral infections, single-nucleotide polymorphisms (SNPs) were genotyped by quantitative polymerase chain reaction in a sample population from Sergipe State, Brazil. This study shows that rs3775291 SNP at Toll-like receptor 3, which triggers type I interferon antiviral responses in mothers infected by Zika virus during pregnancy, is associated with CZS occurrence (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.158-4.148). Moreover, rs1799964 SNP at tumor necrosis factor-α gene in CZS babies is associated with severe microcephaly (OR, 2.63; 95% CI, 1.13-6.21).
Assuntos
Genótipo , Microcefalia/genética , Receptor 3 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Infecção por Zika virus/complicações , Infecção por Zika virus/genética , Adolescente , Adulto , Brasil , Feminino , Técnicas de Genotipagem , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
BACKGROUND Treatment-refractory visceral leishmaniasis (VL) has become an important problem in many countries. OBJECTIVES We evaluated the antimony-resistance mechanisms of Leishmania infantum isolated from VL patients refractory or responsive to treatment with pentavalent antimony. METHODS Strains isolated from antimony-refractory patients (in vitro antimony-resistant isolates) and antimony-responsive patients (in vitro antimony-sensitive isolates) were examined. Morphological changes were evaluated by transmission electron microscopy after trivalent antimony exposure. P-glycoprotein (P-gp) efflux pump activity was evaluated using the pump-specific inhibitor verapamil hydrochloride, and the role of thiol in trivalent antimony resistance was investigated using the enzymatic inhibitor L-buthionine sulfoximine. FINDINGS Antimony treatment induced fewer alterations in the cellular structure of L. infantum resistant isolates than in that of sensitive isolates. P-gp efflux activity was not involved in antimony resistance in these isolates. Importantly, the resistant isolates contained higher levels of thiol compared to the sensitive isolates, and inhibition of thiol synthesis in the resistant isolates recovered their sensitivity to trivalent antimony treatment, and enhanced the production of reactive oxygen species in promastigotes exposed to the drug. MAIN CONCLUSIONS Our results demonstrate that isolates from patients with antimony-refractory VL exhibited higher thiol levels than antimony-sensitive isolates. This indicates that redox metabolism plays an important role in the antimony-resistance of New World VL isolates.
Assuntos
Resistência a Medicamentos , Leishmaniose Visceral/parasitologia , Antimônio/farmacologia , Butionina Sulfoximina , Testes de Sensibilidade Parasitária , Inibidores EnzimáticosRESUMO
BACKGROUND Treatment-refractory visceral leishmaniasis (VL) has become an important problem in many countries. OBJECTIVES We evaluated the antimony-resistance mechanisms of Leishmania infantum isolated from VL patients refractory or responsive to treatment with pentavalent antimony. METHODS Strains isolated from antimony-refractory patients (in vitro antimony-resistant isolates) and antimony-responsive patients (in vitro antimony-sensitive isolates) were examined. Morphological changes were evaluated by transmission electron microscopy after trivalent antimony exposure. P-glycoprotein (P-gp) efflux pump activity was evaluated using the pump-specific inhibitor verapamil hydrochloride, and the role of thiol in trivalent antimony resistance was investigated using the enzymatic inhibitor L-buthionine sulfoximine. FINDINGS Antimony treatment induced fewer alterations in the cellular structure of L. infantum resistant isolates than in that of sensitive isolates. P-gp efflux activity was not involved in antimony resistance in these isolates. Importantly, the resistant isolates contained higher levels of thiol compared to the sensitive isolates, and inhibition of thiol synthesis in the resistant isolates recovered their sensitivity to trivalent antimony treatment, and enhanced the production of reactive oxygen species in promastigotes exposed to the drug. MAIN CONCLUSIONS Our results demonstrate that isolates from patients with antimony-refractory VL exhibited higher thiol levels than antimony-sensitive isolates. This indicates that redox metabolism plays an important role in the antimony-resistance of New World VL isolates.
Assuntos
Antimônio/farmacologia , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/ultraestrutura , Leishmaniose Visceral/parasitologia , Compostos de Sulfidrila/metabolismo , Butionina Sulfoximina/farmacologia , Resistência a Medicamentos , Inibidores Enzimáticos/farmacologia , Humanos , Microscopia Eletrônica de Transmissão , Testes de Sensibilidade ParasitáriaRESUMO
Visceral leishmaniasis (VL) is a systemic transmissible disease that remains to be a major global health problem. The inflammatory response during VL is characterized by the release of several cytokines and other pro-inflammatory mediators. Triggering Receptor Expressed on Myeloid Cells (TREM) are a group of evolutionarily conserved membrane-bound surface receptors expressed on neutrophils and monocytes. Engagement of TREM-1 directs intracellular signaling events that drive cytokine production, degranulation, and phagocytosis. In certain inflammatory-associated diseases, TREM-1 can also be found as a soluble form (sTREM-1), which can negatively regulate TREM-1 receptor signaling. In these studies, we now find that high levels of circulating sTREM-1 correlate directly with VL disease severity. In particular, high levels of sTREM-1 were observed in non-survivor VL patients. Furthermore, these levels of sTREM-1 positively correlated with liver size and negatively correlated with leukocyte counts and hemoglobin concentration. Moreover, we found that neutrophils exposure in vitro to Leishmania infantum modulates TREM-1, DAP12, and IL-8 gene expression, while also increasing release of sTREM-1. Finally, results revealed that higher sTREM-1 levels are associated with increasing parasite ratio. Taken together, these studies suggest that L. infantum may modulate TREM-1 in neutrophils and high levels of this molecule is associated with severe VL.
RESUMO
BACKGROUND: Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L.) infantum is associated with the development and severity of disease. METHODOLOGY/PRINCIPAL FINDINGS: Sera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals. CONCLUSIONS/PRINCIPAL FINDINGS: Although differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L. infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-γ, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-γ, IL-10, IL-6, TNF-α and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum.
Assuntos
Interleucina-27/sangue , Interleucina-6/sangue , Leishmaniose Visceral/sangue , Receptores de Lipopolissacarídeos/sangue , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Leishmania infantum/fisiologia , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Geospatial analysis was used to study the epidemiology of Schistosoma mansoni, intestinal parasites and co-infections in an area (Ilha das Flores) in Sergipe, Brazil. We collected individually georeferenced sociodemographic, behavioral and parasitological data from 500 subjects, analyzed them by conventional statistics, and produced risk maps by Kernel estimation. The prevalence rates found were: S. mansoni (24.0%), Trichuris trichiura (54.8%), Ascaris lumbricoides (49.2%), Hookworm (17.6%) and Entamoeba histolytica (7.0%). Only 59/500 (11.8%) individuals did not present any of these infections, whereas 279/500 (55.8%) were simultaneously infected by three or more parasites. We observed associations between S. mansoni infection and various variables such as male gender, being rice farmer or fisherman, low educational level, low income, water contact and drinking untreated water. The Kernel estimator indicated that high-risk areas coincide with the poorest regions of the villages as well as with the part of the villages without an adequate sewage system. We also noted associations between both A. lumbricoides and hookworm infections with low education and low income. A. lumbricoides infection and T. trichiura infection were both associated with drinking untreated water and residential open-air sewage. These findings call for an integrated approach to effectively control multiple parasitic infections.