Innate Sensing of HIV-Infected Cells

Cell-free HIV-1 virions are poor stimulators of type I interferon (IFN) production. We examined here how HIV-infected cells are recognized by plasmacytoid dendritic cells (pDCs) and by other cells. We show that infected lymphocytes are more potent inducers of IFN than virions. There are target cell-type differences in the recognition of infected lymphocytes. In primary pDCs and pDC-like cells, recognition occurs in large part through TLR7, as demonstrated by the use of inhibitors and by TLR7 silencing. Donor cells expressing replication-defective viruses, carrying mutated reverse transcriptase, integrase or nucleocapsid proteins induced IFN production by target cells as potently as wild-type virus. In contrast, Env-deleted or fusion defective HIV-1 mutants were less efficient, suggesting that in addition to TLR7, cytoplasmic cellular sensors may also mediate sensing of infected cells. Furthermore, in a model of TLR7-negative cells, we demonstrate that the IRF3 pathway, through a process requiring access of incoming viral material to the cytoplasm, allows sensing of HIV-infected lymphocytes. Therefore, detection of HIV-infected lymphocytes occurs through both endosomal and cytoplasmic pathways. Characterization of the mechanisms of innate recognition of HIV-infected cells allows a better understanding of the pathogenic and exacerbated immunologic events associated with HIV infection

Tuberculosis and HIV Co-Infection

Tuberculosis (TB) and HIV co-infections place an immense burden on health care systems and pose particular diagnostic and therapeutic challenges. Infection with HIV is the most powerful known risk factor predisposing for Mycobacterium tuberculosis infection and progression to active disease, which increases the risk of latent TB reactivation 20-fold. TB is also the most common cause of AIDS-related death. Thus, M. tuberculosis and HIV act in synergy, accelerating the decline of immunological functions and leading to subsequent death if untreated. The mechanisms behind the breakdown of the immune defense of the co-infected individual are not well known. The aim of this review is to highlight immunological events that may accelerate the development of one of the two diseases in the presence of the co-infecting organism. We also review possible animal models for studies of the interaction of the two pathogens, and describe gaps in knowledge and needs for future studies to develop preventive measures against the two diseases

Macrophage signaling in HIV-1 infection

The human immunodeficiency virus-1 (HIV-1) is a member of the lentivirus genus. The virus does not rely exclusively on the host cell machinery, but also on viral proteins that act as molecular switches during the viral life cycle which play significant functions in viral pathogenesis, notably by modulating cell signaling. The role of HIV-1 proteins (Nef, Tat, Vpr, and gp120) in modulating macrophage signaling has been recently unveiled. Accessory, regulatory, and structural HIV-1 proteins interact with signaling pathways in infected macrophages. In addition, exogenous Nef, Tat, Vpr, and gp120 proteins have been detected in the serum of HIV-1 infected patients. Possibly, these proteins are released by infected/apoptotic cells. Exogenous accessory regulatory HIV-1 proteins are able to enter macrophages and modulate cellular machineries including those that affect viral transcription. Furthermore HIV-1 proteins, e.g., gp120, may exert their effects by interacting with cell surface membrane receptors, especially chemokine co-receptors. By activating the signaling pathways such as NF-kappaB, MAP kinase (MAPK) and JAK/STAT, HIV-1 proteins promote viral replication by stimulating transcription from the long terminal repeat (LTR) in infected macrophages; they are also involved in macrophage-mediated bystander T cell apoptosis. The role of HIV-1 proteins in the modulation of macrophage signaling will be discussed in regard to the formation of viral reservoirs and macrophage-mediated T cell apoptosis during HIV-1 infection

Examples of the use of optical spectroscopy to detect damage of thermal barrier coatings during cyclic oxidation

This paper describes some examples of the use of two optical spectroscopy techniques to study thermal barrier coating (TBC) degradation preceeding failure. The first part describes photoluminescence piezospectroscopy (PLPS) results obtained on a series of specimens with EB-PVD TBC and Pt -aluminised bond coats. The monotonic decrease of the alumina compressive stress level with ageing and thermal cycling confirms that TGO compressive stress levels can be used as residual life indicators in this type of coating. The automatic mapping system implemented by RSE (Ricerca sul Sistema Energetico) provides precise and reliable results about the level of damage at the BC/TBC interface, well before failure; mapping provides data regarding the precise positions where the first macroscopic detachment (a few millimeters wide) occurs. As PLPS is not applicable to thermal-sprayed APS TBCs, the second part of the paper describes some examples of the contribution that Raman spectroscopy can provide to detect phase changes due to degradation preceeding failure of the TBCs. Possible problems relating to the presence of undesired RE elements in the ceramic layer due to strong fluorescence are also described; solutions are proposed. Finally, examples of how innovative confocal microRaman produces maps evidencing areas where high temperature exposure and thermal cycling-produced phase transformation of the Yttria partially stabilised Zirconia from tetragonal to monoclinic (which typically occurs during cracking processes preceeding final TBC failure) are provided

NOx virtual sensor design via in-cylinder pressure feature extraction

In this paper, a novel approach for NOx generation modeling in heavy-duty (HD) Diesel engines is proposed. Only the indicated pressure and the speed measurements are used, standing on the assumption that all combustion phenomenona are reflected by the crank angle resolved pressure trajectory. A principal component analysis is performed to describe the information included in the pressure by means of a limited set of variables; this enables the use of simple identification techniques to derive a simple and reliable predictor, also suited for on-line estimation. The proposed strategy is implemented on a off-road HD Diesel engine and validated on a standard test cycle

Chloracne following Environmental Contamination by TCDD in Seveso, Italy

Data are presented on the occurrence of chloracne, clinical symptoms and biochemical changes in 164 children following environmental contamination by TCDD from an industrial accident in Seveso, Italy. An overall positive association was found between the territorial distribution of chloracne cases and the different levels of soil contamination in the affected area. Individual risk factors such as condition and length of exposure, intake via contaminated foods, etc. were evaluated; no single factor appeared to be associated with chloracne. Disturbances of the gastrointestinal tract were more frequently observed in children affected with chloracne than in those from the same areas having no skin lesions. However, no clinically definable systemic disease has been diagnosed