EDITOR'S PICK: How STDs increase the risk of becoming infected with HIV
Individuals who have a sexually transmitted disease (e.g., genital herpes, gonorrhea, syphilis, and chlamydia) and women with yeast and bacterial vaginal infections have an increased risk of becoming infected with HIV if exposed to the virus through sexual contact. Although several explanations have been proposed, exactly how and why STDs have this effect has not been clear. Now, Teunis B.H. Geijtenbeek and colleagues, at VU University Medical Center, The Netherlands, have described a way in which STDs can increase acquisition of HIV-1 infection in an ex vivo human skin explant model that they hope might be amenable to therapeutic modulation to prevent HIV transmission.
In the ex vivo human skin explant model, although immature immune cells known as Langerhans cells (LCs) captured HIV, they did not efficiently transmit the virus to T cells, something that is essential for the initiation of full disease. By contrast, efficient virus transmission was observed if LCs were activated by inflammatory stimuli. As the infectious agents that cause the STDs thrush and gonorrhea triggered the same inflammatory stimuli in vaginal and skin explants, the authors suggest that in the presence of an STD-causing infectious agent, LCs might become activated, thereby increasing an individual's risk of becoming infected with HIV. Further, these data suggest that antiinflammatory therapies might provide a way to prevent HIV transmission.
TITLE: TNF-alpha and TLR agonists increase susceptibility to HIV-1 transmission by human Langerhans cells ex vivo
Teunis B.H. Geijtenbeek
VU University Medical Center, Amsterdam, The Netherlands.
Phone: (31) 20-4448080; Fax: (31) 20-4448081; E-mail: T.Geijtenbeek@vumc.nl.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34721
VIROLOGY: HIV-stimulated immune cells generate cells with immunosuppressive properties
Nina Bhardwaj and colleagues, at New York University, have provided new insight into the role of human immune cells known as plasmacytoid dendritic cells (pDCs) in the anti-HIV immune response.
When pDCs interact with HIV they become activated, secreting large amounts of the soluble factor IFN-alpha, which is a key component of the anti-HIV immune response. But, in in vitro studies, the authors found that HIV-1–stimulated human pDCs induced uncommitted CD4+ T cells to become Tregs, which are T cells that suppress immune responses. Further analysis indicated that pDC-induced Tregs inhibited the in vitro maturation of bystander conventional dendritic cells (which are cells central to the initiation of immune responses), providing insight into one mechanism by which these cells could dampen the anti-HIV immune response. These data indicate that pDCs have two distinct roles in the anti-HIV immune response: they potentiate the anti-HIV immune response via the production of IFN-alpha and are likely to limit excessive immune activation (which can be harmful) via the induction of Tregs.
TITLE: HIV-activated human plasmacytoid DCs induce Tregs through an indoleamine 2,3-dioxygenase–dependent mechanism
New York University, New York, New York. USA.
Phone: (212) 263-5814; Fax: (212) 263-6729; E-mail: Nina.Bhardwaj@nyumc.org.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34823
ONCOLOGY: How immune cells help tumors grow blood vessels
Data published over the past few years indicate that some cells of the immune system, in particular cells known as myeloid cells, have a role in promoting cancer progression. This is, in part, because they promote the development of new blood vessels (a process known as angiogenesis) that provide the tumor with the nutrients it needs to grow. New results, generated by Hua Yu and colleagues, at City of Hope National Medical Center, Duarte, have implicated a role for the protein Stat3 in the induction of tumor angiogenesis by tumor-associated myeloid cells in mice.
Previous studies have shown that constitutively activated Stat3 in tumor cells has a role in promoting tumor angiogenesis. In the study, it was found that Stat3 is also constitutively activated in myeloid cells isolated from mouse tumors and that these cells could induce angiogenesis in vitro, because the constitutively activated Stat3 induced the cells to produce angiogenic factors. Further analysis indicated that constitutively activated Stat3 also induced tumor cells and tumor-associated myeloid cells to produce factors that induced endothelial cells to express Stat3 and that this was important for promoting angiogenesis in vitro. Consistent with the conclusion that constitutive activation of Stat3 in tumor-associated myeloid cells is important for tumor angiogenesis, if the myeloid cells expressed no Stat3 tumor angiogenesis was markedly decreased.
TITLE: Stat3 mediates myeloid cell–dependent tumor angiogenesis in mice
City of Hope National Medical Center, Duarte, California, USA.
Phone: (626) 471-7238; Fax: (626) 256-8708; E-mail: firstname.lastname@example.org.
View the PDF of this article at: https://www.the-jci.org/article.php?id=35213
METABOLIC DISEASE: Type 2 diabetes under stress
Type 2 diabetes is caused by an inability of the beta-cells in the pancreas to produce enough of the hormone insulin to meet the body's needs. Central to this is a loss of beta-cell function and mass as a result of insulin resistance (the inability of cells in the body to respond appropriately to insulin). New insight into how insulin resistance leads to loss of beta-cell mass has now been provided by studies in multiple mouse models of type 2 diabetes performed by Randal Kaufman and colleagues, at the University of Michigan Medical School, Ann Arbor.
In the study, in the absence of the protein CHOP, the symptoms of diabetes improved in two mouse models of the disease, and this was associated with increased beta-cell mass. In addition, the structure of the beta-cells appeared to be more normal and they were encouraged to survive. CHOP is a protein that is involved in promoting the death of a cell that is under stress because it is producing more protein than it is able to handle. The authors therefore propose that insulin resistance causes beta-cells to make more insulin than they can handle, such that the stress signaling pathways that activate CHOP are initiated and the beta-cells die, thereby decreasing beta-cell mass. Further, it is suggested that drugs that modulate the stress response to over production of insulin might provide a new approach to the treatment of type 2 diabetes.
TITLE: Chop deletion reduces oxidative stress, improves beta-cell function, and promotes cell survival in multiple mouse models of diabetes
Randal J. Kaufman
University of Michigan Medical School, Ann Arbor, Michigan, USA.
Phone: (734) 763-9037; Fax: (734) 763-9323; E-mail: email@example.com.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34587
VASCULAR BIOLOGY: Stuck on you: FGF proteins help ensure cells lining blood vessels stick together
Very little is known about the molecules and signaling pathways responsible for maintaining our network of blood vessels. However, work in a number of different in vitro cells lines and animal models, by Michael Simons and colleagues, at Dartmouth Medical School, Lebanon, and Yale University School of Medicine, New Haven, has indicated that signaling pathways initiated by a family of proteins known as the FGF family have a key role in maintaining blood vessel integrity. Specifically, the authors found that disruption of signaling pathways initiated by the FGF family in bovine and human endothelial cells (the cells that line blood vessels) in vitro and in adult mouse and rat endothelial cells in vivo ultimately resulted in the disintegration of the blood vessels. Further analysis revealed that, in the absence of signaling initiated by the FGF family, the complexes that hold endothelial cells together fell apart, leading to loss of endothelial cells.
TITLE: The FGF system has a key role in regulating vascular integrity
Yale University School of Medicine, New Haven, Connecticut, USA.
Phone: (203) 785-7000; Fax: (203) 785-7144; E-mail: firstname.lastname@example.org.
View the PDF of this article at: https://www.the-jci.org/article.php?id=35298
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