Paracoccidioidomycosis is a systemic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. Its major antigen is a 43 kDa glycoprotein whose peptides embody different functions: P10 peptide, a T-cell epitope, induces protective response while P4 and P23 peptides inhibit both, macrophage functions and inflammatory reaction, thus facilitating infection. Here we ...

Introduction:Propylene glycol (PG) is a common solvent used in medical preparations. It is generally recognized as safe at regulated concentrations; however, its apoptotic potential is unknown.Results:PG triggered widespread apoptotic neurodegeneration with the greatest damage at postnatal day 7 (P7). Significant apoptosis was observed at doses as low as 2 ml/kg. ...

BACKGROUND:: Supplementation studies of glutamine, arginine and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates. However, the potential for a more stable and soluble dipeptide, Arginyl-Glutamine (Arg-Gln) or DHA with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln ...

HIV-1 transactivator protein, Tat, has been identified as an activator of HIV-1 replication. It also dysregulates cytokine production and apoptosis in T-cells. Of the various cell death processes, autophagy is a self-digestion and degradation mechanism that recycles the contents of the cytosol, including macromolecules and cellular organelles, resulting in self-repair ...

Accumulating evidence suggests that the amino acid glutamate (Glu) may play a role in mediating immune function. The demonstration of Glu receptors (GluR) and Glu transporters (GluT) on a variety of immune cells suggests that Glu has a functional role in immunoregulation well beyond its role as a neurotransmitter. The ...

Abstract The purpose of this study was to determine if switching to an Lopinavir/ritonavir (LPV/r)-containing regimen resulted in greater immune reconstitution in patients with immunologic failure despite complete viral suppression with highly active antiretroviral therapy (HAART). Twenty patients with partial or no immune response to HAART despite viral suppression were ...

The presence of human immunodeficiency virus (HIV)-infected macrophages in the parenchyma of central nervous system is an hallmark of acquired immunodeficiency syndrome-related neuroinflammation. Once penetrated the blood-brain barrier (BBB), macrophages closely interact with astrocytes, beginning with those lying beneath the BBB endothelium. By investigating the consequences of the cell-cell interaction ...

Inflammation is a broad term for what happens in the body when the immune system is activated to counter a threat. A healthy immune response is key to good health, but ongoing immune activation and inflammation due to a persistent threat such as chronic HIV infection can lead to many ...

One of the hallmarks of Human Immunodeficiency Virus-1 (HIV-1) infection is progressive depletion of the infected and bystander CD4+ T-cells by apoptosis. Different mitochondrial proteins have been implicated in this apoptotic process; however, the role of different subunits of mitochondrial oxidative phosphorylation (OXPHOS) complexes in apoptosis is not clearly understood. ...

The rapid induction of type I interferon (IFN) is essential for establishing innate antiviral responses. During infection, cytoplasmic viral RNA is sensed by two DExD/H box RNA helicases, RIG-I and MDA5, ultimately driving IFN production. Here, we demonstrate that purified genomic RNA from HIV-1 induces a RIG-I-dependent type I IFN ...

Dendritic cells (DC) are the most potent antigen-presenting cells, and form a link between the innate and adaptive immune system. They sample the periphery of the body for antigens and present them to T cells to elicit a proper immune response. It has been shown that dendritic cells phagocytose mycobacteria, ...

Recent studies provide compelling evidence that HIV-1 entry in cell lines and lymphocytes proceeds by endocytosis, but these studies are still lacking in macrophages, an important natural target cell for HIV-1. Macrophages exhibit continual and extensive endocytic activity as part of their natural functions, so we investigated the uptake pathways ...

Kaposi sarcoma (KS) occurs as a result of Kaposi sarcoma-associated herpesvirus (KSHV) infection, typically in the context of an immunodeficient state such as coinfection with HIV or transplantation. Systemic treatment of KS has traditionally involved one of several chemotherapeutic agents either in combination or as single agents, which typically provides ...

HIV-1 can establish both long lived and productive infection of macrophages (Mϕ) but circulating monocytes are less permissive to infection. Multiple studies have identified extensive changes to monocyte and Mϕ phenotype, differentiation or function. These include alterations in Toll-like receptor signaling and resultant changes to cytokine responses, specific defects in ...

Microbial translocation from the gastrointestinal tract has been implicated in chronic activation of the immune system during progressive HIV-1 infection by ill-defined mechanisms. We recently identified a gene encoding syndecan-1 (SYN1) in microarray studies of HIV-1 infection in lymphatic tissues and show here that increased expression of SYN1 in the ...

CD8(+) T-lymphocytes can utilize noncytolytic mechanisms to suppress HIV-1 replication through the secretion of soluble factors. The secretion of MIP-1β, MIP-1α, IP-10, MIG, IL-1α, and interferon gamma correlated most strongly with soluble noncytolytic suppression (p<0.0001). Since the noncytolytic response is impaired by histone hyperacetylation, we examined the ability of histone ...

Infection with human immunodeficiency virus (HIV)-1 induces a progressive deterioration of the immune system that ultimately leads to acquired immune deficiency syndrome (AIDS). Murine models indicate that the common γ-chain (γ(c))-sharing cytokine interleukin (IL)-21 and its receptor (IL-21R) play a crucial role in maintaining polyfunctional T cell responses during chronic ...

There is growing evidence that highlights the role of the immune response during acute human immunodeficiency virus type 1 (HIV-1) infection in the control or development of disease. The adaptive immune responses do not appear until after HIV-1 infection is already well established, so the role of earlier and faster-responding ...

We biochemically simulated HIV-1 DNA polymerization in physiological nucleotide pools found in two HIV-1 target cell types: terminally differentiated/non-dividing macrophages and activated/dividing CD4(+) T cells. Quantitative tandem mass spectrometry shows that macrophages harbor 22-320-fold lower dNTP concentrations and a greater disparity between ribonucleoside triphosphate (rNTP) and dNTP concentrations than dividing ...

Dendritic cells serve a key function in host defence, linking innate detection of microbes to activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of human immunodeficiency virus (HIV) by host innate pattern-recognition receptors and subsequent coupling to antiviral T-cell responses is not yet known. Dendritic cells are ...

The transactivator protein Tat of human immunodeficiency virus type 1 (HIV-1) is known to suppress microtubule dynamics and thereby trigger apoptosis in T lymphocytes. These actions of Tat constitute one of the major mechanisms for the massive destruction of T lymphocytes associated with the acquired immunodeficiency syndrome. Herein, we show ...

Vitamin-D-receptor (VDR) mediates immunomodulatory effects of vitamin-D₃ (VD₃). The VDR-rs1544410_GG polymorphism has been associated with delayed progression rates to AIDS and resistance to HIV-1 infection. The aim of the present study was to investigate differences in VD₃ mediated effects on rs1544410 genotyped dendritic cells (DCs) and macrophages (MDM), key cells ...

Microbial translocation contributes to immune activation and disease progression during chronic human immunodeficiency virus type 1 (HIV-1) infection. However, its role in the African AIDS epidemic remains controversial. Here, we investigated the relationship between markers of monocyte activation, plasma lipopolysaccharide (LPS), and HIV-1 RNA in South Africans prioritized to receive ...

Background: Numerous evidences indicate that in some HIV-1 positive patients, the humoral and cellular immune responses are induced against HIV-1 proteins and this is inversely related to the progress of infection. Objective: The aim of this study was the evaluation of the Adenovectors containing HIV genes in induction of immune ...

Protection from primary human immunodeficiency virus type 1 (HIV-1) infection has not yet been accomplished by vaccines inducing HIV-1-specific acquired immunity. Nevertheless, it has been reported that a small subgroup of women remain resistant to HIV-1 infection under natural conditions. If similar conditions can be induced in uninfected individuals, it ...

Chronic HIV-1 infection is associated with excessive immune activation and immune exhaustion. We investigated the relationship of these 2 phenotypes and frequency of regulatory T cells (Tregs) in controlled and uncontrolled chronic HIV-1 infection. Immune exhaustion marker PD-1, its ligand PD-L1, CD4CD25 FoxP3 Tregs, HLA-DR, and CD38 coexpression as activation ...

To characterize the homeostasis of CD4FoxP3 regulatory T cells (Treg) and its association with immune hyperactivation in the disease progression of chronic HIV-1 infection. Treg proliferation and apoptosis markers were determined and the relation to disease progression and Treg activation was analyzed. Fifty-six HIV-1-infected highly active antiretroviral therapy (HAART)-naive subjects ...

Retroviruses have evolved effective strategies to evade the host immune response, such as high variability and latent infection. In addition, primate lentiviruses, such as HIV-1, have acquired several "accessory" genes that antagonize antiviral host restriction factors and facilitate viral immune evasion, thereby allowing continuous and efficient viral replication despite apparently ...

HIV-1 replication within macrophages of the CNS often results in cognitive and motor impairment, which is known as HIV-associated dementia (HAD) in its most severe form. IFN-beta suppresses viral replication within these cells during early CNS infection, but the effect is transient. HIV-1 eventually overcomes this protective innate immune response ...

This study was designed to evaluate which of several T-cell-specific, immune response assays are the most relevant in measuring the key characteristics of an effective immune response to HIV-1. Using 5 HIV-1 antigens as stimulants, we assessed lymphocyte proliferation, supernatant gamma interferon (IFN-gamma) cytokine production (CP), single-cell IFN-gamma production by ...

Although oral coinfections (e.g., periodontal disease) are highly prevalent in human immunodeficiency virus type 1-positive (HIV-1(+)) patients and appear to positively correlate with viral load levels, the potential for oral bacteria to induce HIV-1 reactivation in latently infected cells has received little attention. We showed that HIV-1 long terminal repeat ...

Human immunodeficiency virus type 1 (HIV-1) is commonly associated with immune dysfunctions and the suppression of antigen-presenting cells. This results in immune alterations, which could lead to impaired neuronal functions, such as neuroAIDS. The neurotoxic factor kynurenine (KYN), the rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO), serotonin (5-HT), and serotonin transporter (5-HTT) ...

HIV-1-infected opiate abusers often exhibit an accelerated form of HIV-1-associated dementia and enhanced neurological dysfunction. Productive HIV-1 infection of microglia and perivascular macrophages and the resultant secretion of neurotoxic molecules by these cells contribute to this phenomenon. In order to understand the role of morphine in this process, we performed ...

MicroRNAs (miRNAs) are a class of small RNA molecules that function to control gene expression and restrict viral replication in host cells. The production of miRNAs is believed to be dependent upon the DICER enzyme. Available evidence suggests that in T lymphocytes, HIV-1 can both suppress and co-opt the host's ...

Pattern recognition receptors (PRRs) play a pivotal role in host innate immune responses against microbial infection. Viruses are primarily recognized by PRRs such as Toll-like receptor 3, 7, 8 and 9, and RIG-I-like receptors. Recent studies have demonstrated that DNA-dependent activator of IFN-regulatory factors (DAI) is a cytosolic sensor molecule ...

While CCR5 is the principal coreceptor used by macrophage (M)-tropic HIV-1, not all primary CCR5-using (R5) viruses enter macrophages efficiently. Here, we used functionally-diverse R5 envelope (Env) clones to characterize virus-cell interactions important for efficient CCR5-mediated macrophage entry. The magnitude of macrophage entry by Env-pseudotyped reporter viruses correlated with increased ...

Dendritic cells (DCs) play an important role in viral infections both as initiators of immunity and as viral targets. Interaction between DCs and the innate-like CD1d-restricted natural killer T (NKT) cells results in the mutual activation of both cells and the subsequent initiation of cellular immune responses. Here, we show ...

Recently, a mechanism of negative regulation of immune responses by a specialized population of so-called regulatory T cells (Tregs) has become a focus of intense investigation. Through the discovery of transcription factor Foxp3 as a central molecular determinant of Tregs differentiation and function, the complex biology of these cells, including ...

HIV-1 replication and microbial translocation occur concomitant with systemic immune activation. This study delineates mechanisms of immune activation and CD4 T-cell decline in pediatric HIV-1 infection. Cross-sectional and longitudinal cellular and soluble plasma markers for inflammation were evaluated in 14 healthy and 33 perinatally HIV-1-infected pediatric study volunteers prior to ...

All primate lentiviruses encode Nef, an accessory protein that is important for viral pathogenicity in vivo. Lentiviral Nef proteins regulate the release of chemokines (MIP-1 alpha/beta) from infected macrophages, thereby enhancing virus dissemination (S. Swingler, A. Mann, J. Jacque, B. Brichacek, V. G. Sasseville, K. Williams, A. A. Lackner, E. ...

The V3 region of the HIV-1 envelope (Env) glycoprotein gp120 is a key functional domain yet it exhibits distinct mutational patterns across subtypes. Here an invariant residue (Ile 309) was replaced with Leu in 7 subtype C patient-derived Envs from recent infection and 4 related neutralizing antibody escape variants that ...

Macrophages are a major target of HIV-1 infection. HIV-1-infected macrophages form multinucleated giant cells (MGCs) using poorly elucidated mechanisms. In this study, we show that MGC formation was reduced when human macrophages were infected with nef-deleted HIV-1. Moreover, expression of Nef, an HIV-1 protein required in several aspects of AIDS, ...

The development of effective microbicides for the prevention of HIV-1 sexual transmission represents a primary goal for the control of AIDS epidemics worldwide. A promising strategy is the use of bacteria belonging to the vaginal microbiota as live microbicides for the topical production of HIV-1 inhibitors. We have engineered a ...

Induction of type I interferons (IFN) is a central feature of innate immune responses to microbial pathogens and is mediated via Toll-like receptor (TLR)-dependent and -independent pathways. Prothymosin-alpha (ProTalpha), a small acidic protein produced and released by CD8(+) T cells, inhibits HIV-1, although the mechanism for its antiviral activity was ...

HIV-associated nephropathy (HIVAN) is the most common cause of end-stage renal disease in persons with HIV/AIDS and is characterized by focal glomerulosclerosis and dysregulated renal tubular epithelial cell (RTEC) proliferation and apoptosis. HIV-1 viral protein r (Vpr) has been implicated in HIV-induced RTEC apoptosis but the mechanisms of Vpr-induced RTEC ...

Engagement of CD40 with CD40L induces dendritic cell (DC) maturation and activation, thereby promoting immune responses. The objective of this study was to investigate whether immunization with chimeric CD40L/SHIV virus-like particles (CD40L/SHIV-VLP) could enhance immune responses to SIV Gag and HIV Env proteins by directly activating DCs. We found that ...

A host genetic variant (-35C/T) correlates with increased human leukocyte antigen C (HLA-C) expression and improved control of HIV-1. HLA-C-mediated immunity may be particularly protective because HIV-1 is unable to remove HLA-C from the cell surface, whereas it can avoid HLA-A- and HLA-B-mediated immunity by Nef-mediated down-modulation. However, some individuals ...

Dendritic cells (DCs) in mucosal surfaces are early targets for human immunodeficiency virus-1 (HIV-1). DCs mount rapid and robust immune responses upon pathogen encounter. However, immune response in the early events of HIV-1 transmission appears limited, suggesting that HIV-1 evade early immune control by DCs. We report that HIV-1 induces ...

Primary immunodeficiencies are congenital defects that affect formation or function of the immune system. Congenital immunodeficiency should be considered as a differential diagnosis for repeated infections in a young animal. Defects in the immune system may lead to complete or partial loss of immunity. Some animals with mild immunodeficiency can ...

CD4(+) T cell lymphocytes are a major target for human immunodeficiency virus type-1 (HIV-1) infection. During this chronic infection, CD4(+) T cell loss (induced through direct viral replication), generalized immune activation and increased susceptibility to apoptosis result in impaired T cell homeostasis with subsequent development of opportunistic infections and cancers. ...