HIV-1 Infection of DC: Evidence for the Acquisition of Virus Particles from Infected T Cells by Antigen Uptake Mechanism

Dendritic cells (DC) play a pivotal role in transmission and dissemination of HIV-1. Earlier studies reported that DC present at the site of infection trap virus particles via DC-SIGN and transfer the virus to the interacting naïve T cells. This prompted us to ask the question whether DC could acquire virus from infected T cells during DC-T cell interaction. To address this, we investigated the likely transfer of virus from HIV-1 infected T cells to DC and the underlying mechanisms involved. Results indicate that DC acquire virus from infected T cells via antigen uptake mechanism and this results in infection of DC with expression of proteins directed by viral DNA. Further studies with HIV-1 lacking the Env protein also resulted in infection of DC. The use of antibodies against DC-SIGN and DC-SIGN-R ruled out a role for receptor in the infection of DC. Additional data show that DC infection is directly correlated with the ability of DC to take up antigen from infected T cells. Overall, these studies provide evidence to suggest that HIV-1, besides infecting immune cells, also utilizes immunological mechanism(s) to acquire and disseminate virus

HIV-1 Promotes Intake of Leishmania Parasites by Enhancing Phosphatidylserine-Mediated, CD91/LRP-1-Dependent Phagocytosis in Human Macrophages

Over the past decade, the number of reported human immunodeficiency virus type-1 (HIV-1)/Leishmania co-infections has risen dramatically, particularly in regions where both diseases are endemic. Although it is known that HIV-1 infection leads to an increase in susceptibility to Leishmania infection and leishmaniasis relapse, little remains known on how HIV-1 contributes to Leishmania parasitaemia. Both pathogens infect human macrophages, and the intracellular growth of Leishmania is increased by HIV-1 in co-infected cultures. We now report that uninfected bystander cells, not macrophages productively infected with HIV-1, account for enhanced phagocytosis and higher multiplication of Leishmania parasites. This effect can be driven by HIV-1 Tat protein and transforming growth factor-beta (TGF-β). Furthermore, we show for the first time that HIV-1 infection increases surface expression of phosphatidylserine receptor CD91/LRP-1 on human macrophages, thereby leading to a Leishmania uptake by uninfected bystander cells in HIV-1-infected macrophage populations. The more important internalization of parasites is due to interactions between the scavenger receptor CD91/LRP-1 and phosphatidylserine residues exposed at the surface of Leishmania. We determined also that enhanced CD91/LRP-1 surface expression occurs rapidly following HIV-1 infection, and is triggered by the activation of extracellular TGF-β. Thus, these results establish an intricate link between HIV-1 infection, Tat, surface CD91/LRP-1, TGF-β, and enhanced Leishmania phosphatidylserine-mediated phagocytosis

Leishmania infantum Amastigotes Enhance HIV-1 Production in Cocultures of Human Dendritic Cells and CD4+ T Cells by Inducing Secretion of IL-6 and TNF-α

Visceral leishmaniasis (VL) is a potentially deadly parasitic disease afflicting millions worldwide. Although itself an important infectious illness, VL has also emerged as an opportunistic disease among patients infected with HIV-1. This is partly due to the increasing overlap between urban regions of high HIV-1 transmission and areas where Leishmania is endemic. Furthermore, VL increases the development and clinical progression of AIDS-related diseases. Conversely, HIV-1-infected individuals are at greater risk of developing VL or suffering relapse. Finally, HIV-1 and Leishmania can both productively infect cells of the macrophage-dendritic cell lineage, resulting in a cumulative deficiency of the immune response. We therefore studied the effect of Leishmania infantum on HIV-1 production when dendritic cells (DCs) are cocultured with autologous CD4+ T cells. We show that amastigotes promote virus replication in both DCs and lymphocytes, due to a parasite-mediated production of soluble factors by DCs. Micro-beads array analyses indicate that Leishmania infantum amastigotes infection induces a higher secretion of several cytokines in these cells, and use of specific neutralizing antibodies revealed that the Leishmania-induced increase in HIV-1 replication is due to IL-6 and TNF-α. These findings suggest that Leishmania's presence within DC/T-cell conjugates leads to an enhanced HIV-1 production

Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells

<p>Abstract</p> <p>Background</p> <p>Microglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS). Leukotriene B₄(LTB₄) and cysteinyl-leukotrienes such as LTC₄are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs) in HIV-1 infection of microglial cells.</p> <p>Methods</p> <p>To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis) were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2) or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR).</p> <p>Results</p> <p>We report in this study that virus replication is reduced upon treatment of MDMis with LTB₄and LTC₄. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5) surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C.</p> <p>Conclusions</p> <p>These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.</p

Hand hygiene education of Greek medical and nursing students: A cross-sectional study

Aim: To investigate medical and nursing students’ education on hand hygiene, their attitude on hand hygiene education and how this education influences their hand hygiene knowledge and practices. Background: Hospital-acquired infections are associated with prolonged hospitalisation and mortality. The most effective measure for their control is healthcare workers’ hand hygiene compliance. Since medical and nursing students constitute the future healthcare workers, our study focuses on them. Design: Cross-sectional study Methods: This study was conducted during the academic year 2016–2017, using a modified World Health Organisation questionnaire. Our sample consisted of 132 medical and 111 nursing students from National and Kapodistrian University of Athens, Greece. In data analysis, the Mann-Whitney and Fisher&apos;s exact tests were applied to compare differences in continuous variables and proportions in categorical variables, respectively. Knowledge and practices overall scores were calculated per student group. Multiple linear regression analyses were performed to assess the influence of potential confounders on these scores. Results: We found that 73.1% of medical and 98.2% of nursing students had received relevant education, which was reported as “only theoretical” by 77.4% of the former and as “hands-on and theoretical” by 88.1% of the latter group. Besides the risk of infection, knowledge acquired in lectures and trainer&apos;s behaviour were also considered very influential factors shaping hand hygiene attitude in both groups. Overall, medical students reported better hand hygiene practices than nursing ones (69.9% and 59.7%, respectively; p &lt; 0.001). The opposite finding was observed regarding their overall knowledge on hand hygiene (57.2% of medical versus 60.4% of nursing students, p = 0.04). The majority of students (86.6% of all participants; p &lt; 0.001) supported the inclusion of compulsory hand hygiene education in their curriculum. Compulsory education and seminars were assessed as the most effective measures to increase hand hygiene compliance (71.4% of all students). Conclusion: In our study, medical students scored better in practices questions than nursing students; this did not apply for the knowledge score. The majority of students supported the inclusion of compulsory education on hand hygiene principles in their Departments’ curricula, highlighting compulsory education and seminars as the most effective measures to increase compliance with hand hygiene. © 2021 Elsevier Lt

Imidazolium-based titanium substrates against bacterial colonization

International audienceNosocomial infections are often induced by the presence of pathogenic organisms on the surface of medical devices or hospital equipment. Chemical modifications of the surface are recognized as efficient strategies to prevent bacterial adhesion but they may have a negative impact on the material's interaction with living tissues. Here we have developed a photoactivated method for the modification of titanium substrates. A photoinduced technique employing a grafting-onto process has been successfully performed to covalently anchor an imidazolium-derivative siloxane onto titanium surfaces. Imidazolium surfaces showed higher bacteria-repellency performances than native titanium substrates, achieving more than 98% anti-adhesion efficiency against Escherichia coli after 24 h of incubation. In addition, these surfaces allowed for the adhesion and viability of osteoblasts cells without evidence of cytotoxicity