transforming-growth-factor-beta and Opportunistic-Infections

Transforming growth factor beta (TGF-beta) family is recognised as one of the major regulators of immune response. Increased synthesis of TGF-beta has been linked to immune defects associated with malignancy and autoimmune disorders, to susceptibility to opportunistic infection, and to fibrotic disease. It is widely believed that this factor is related to the development of two main features of chronic graft dysfunction and rejection, namely fibrosis and atherosclerosis. Studies of haematopoietic pathologies involving TGF-beta have provided an important evidence of its key role in regulation of haematopoiesis. Recent studies have indicated that TGF-beta may be a significant mediator of the profound and prolonged immunosuppression found during graft versus host disease (GVHD) after allogeneic haematopoietic stem cell transplantation. It has also been linked with scleroderma-like features often described in chronic GVHD. Moreover, particular TGF-beta polymorphisms may be prognostic factors in predicting a post-transplant outcome.

Topics: Autoimmune Diseases; Autoimmunity; Fibrosis; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Opportunistic Infections; Transforming Growth Factor beta; Transplantation Immunology

Transforming growth factor-β (TGF-β) has been associated with numerous human infections, but its role in the occurrence of opportunistic infection (OI) after solid organ transplantation remains unexplored. This study aimed to assess the utility of the TGF-β following in vitro stimulation of whole peripheral blood (WPB) as a surrogate biomarker of post-transplant OI in a cohort of liver and kidney recipients. Thirty liver and thirty-one kidney transplant recipients were recruited to be prospectively monitored for one-year post-transplantation. Enzyme-linked immunosorbent assay (ELISA) was performed to calculate IFN-γ, IL-17, IL-10 and TGF-β concentration in the supernatant from the activated WPB. Recipients showed higher TGF-β concentrations compared to IFN-γ, IL-17, IL-10 at baseline, although these differences were not significant between INF and NoINF. However, recipients who developed an OI within the first sixth months had a higher concentration of TGF-β than those without OI. A concentration of TGF-β > 363.25 pg/ml in liver and TGF-β > 808.51 pg/ml in kidney recipients were able to stratify patients at high risk of OI with a sensitivity and specificity above 70% in both types of solid organ transplantations. TGF-β could provide valuable information for the management of liver and kidney recipients at risk of post-transplant infection.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Cytokines; Female; Graft Rejection; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Postoperative Complications; Sensitivity and Specificity; Transforming Growth Factor beta; Young Adult

Although the esophagus is a common site of opportunistic infection in AIDS patients, little is known about the impact of HIV as well as opportunistic infection in the esophageal mucosa. Our aim is to analyze the esophageal immune profile in HIV+ patients with different immunological status with and without the opportunistic Candida infection.. Immunohistochemistry to CD4. Esophageal CD4

Topics: Adult; Candidiasis; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Esophageal Mucosa; Esophagitis; Female; HIV Infections; Humans; Interleukin-17; Interleukin-6; Male; Middle Aged; Opportunistic Infections; Transforming Growth Factor beta

Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-Osler-Weber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Eng(fl/fl)LysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Eng(fl/fl)LysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients.

Topics: Activin Receptors, Type I; Activin Receptors, Type II; Animals; Endoglin; Flow Cytometry; Gene Expression Regulation; Humans; Immunity, Innate; Inflammation; Intracellular Signaling Peptides and Proteins; Macrophages; Mice; Mice, Knockout; Opportunistic Infections; Phagocytosis; Telangiectasia, Hereditary Hemorrhagic; Transforming Growth Factor beta