ABSTRACT
Immune cells can optimize the management of metabolic resources to balance their energy requirements in order to regulate immune responses. The interconnection between immunometabolism and fungal infections is becoming increasingly apparent. Using proteome and metabolome assays, we found that stimulation of primary human monocytes by Candida albicans was accompanied by upregulation of glucose transporter 3 (GLUT3) and activation of the glycerophospholipid metabolism pathway. Upregulated GLUT3 expression has been preliminarily confirmed in monocytes from patients with C. albicans bloodstream infection. Our findings support the importance of GLUT3 in the complex network of glycerophospholipid metabolism and the innate immune responses against C. albicans. In summary, this study might contribute to decipher the regulatory mechanism between the monocyte metabolic reprogramming and innate immune response and reveal potential targets for the antifungal treatments.
Subject(s)
Candida albicans , Immunity, Innate , Glycerophospholipids , Humans , Lipid Metabolism , MonocytesABSTRACT
OBJECTIVE: To retrospectively analyze the cytomegalovirus (CMV) antigenemia test and re-test after antiviral chemotherapy in patients with autoimmune and non-autoimmune diseases. METHODS: CMV Brite kit and indirect immunofluorescence were used to detect CMVpp65 antigenemia in 6471 peripheral blood leukocyte specimens from 5325 clinic and hospitalized patients with clinically suspicious CMV infections from May 2008 to February 2012. And the positive results were defined as episodes of systemic CMV activity. RESULTS: In 6471 EDTA-treated peripheral blood specimens, 948 (14.6%) were found with positive CMV antigenemia. The average positive rate from 13 kinds of autoimmune diseases was 34.9% (670/1922) in which systemic lupus erythematosus patients had the highest (52.4%, 551/1052). Meanwhile, the average positive rate from 12 kinds of non-autoimmune diseases was only 6.1% (144/2367) in which it was 17.3% (27/156) in patients with respiratory/acute renal failure, acquired immunodeficiency syndrome (AIDS) and kidney transplant recipients. And 189 patients with positive antigenemia were re-tested after antiviral chemotherapy and only 64 (33.9%) were converted negatively. CONCLUSIONS: Patients with autoimmune diseases have replaced traditionally immunocompromised patients, e.g. AIDS and kidney transplant recipient, to become the highest risk group of systemic CMV activity. Negative conversion rate of CMV antigenemia is low after antiviral chemotherapy.
Subject(s)
Antigens, Viral/blood , Autoimmune Diseases/complications , Cytomegalovirus Infections/complications , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Autoimmune Diseases/blood , Autoimmune Diseases/drug therapy , Child , Child, Preschool , Cytomegalovirus , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/drug therapy , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
In this study, we investigated the effects of the anti-leukemia drug Harringtonine (HT) on the levels of centromere proteins and gene expression of centromere protein CenpB in L1210 cells. The intensity of centromere fluorescence, shown by indirect immunofluorescence staining, decreased with HT treatment. Western blot showed that the anti-centromere antibody (ACA) serum used in this study recognized 8 proteins with different molecular weights: 140, 80, 70, 56, 37, 34, 32 and 17 kD. The amounts of some of these proteins were reduced to different extents by HT treatment. The ACA antibodies that recognized the 17, 80 and 140 kD proteins in L1210 cells also cross-reacted with 3 proteins with similar molecular weights which are known to be CenpA, CenpB and CenpC, respectively. Northern and Dot blot analyses revealed that the level of CenpB mRNA in HT-treated cells was markedly lower than that in the untreated cells. These results suggest that HT may cause a decrease in the intracellular level of some centromere proteins, probably by inhibiting mRNA expression of corresponding genes. Moreover, it is possible that the cell-killing and appotosis-inducing effects of HT may be mediated by the inhibition of the expression of CenpB and other centromere protein genes.
