Usefulness of Route of Transmission, Absolute CD8+ T-Cell Counts, and Levels of Serum Tumor Necrosis Factor Alpha as Predictors of Survival of HIV-1-Infected Patients with Very Low CD4+ T-Cell Counts

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) plays a crucial role in viral replication and pathogenesis by inducing cell cycle arrest, apoptosis, translocation of preintegration complex, potentiation of glucocorticoid action, impairment of dendritic cell (DC) maturation, and T-cell activation. Recent studies involving the direct effects of Vpr on DCs and T cells indicated that HIV-1 containing Vpr selectively impairs phenotypic maturation, cytokine network, and antigen presentation in DCs and dysregulates costimulatory molecules and cytokine production in T cells. Here, we have further investigated the indirect effect of HIV-1 Vpr+ virus-infected DCs on the bystander CD8+ T-cell population. Our results indicate that HIV-1 Vpr+ virus-infected DCs dysregulate CD8+ T-cell proliferation and induce apoptosis. Vpr-containing virus-infected DC-mediated CD8+ T-cell killing occurred in part through enhanced tumor necrosis factor alpha production by infected DCs and subsequent induction of death receptor signaling and activation of the caspase 8-dependent pathway in CD8+ T cells. Collectively, these results provide evidence that Vpr could be one of the important contributors to the host immune escape by HIV-1 through its ability to dysregulate both directly and indirectly the DC biology and T-cell functions.

Download Full-text

Association between serum tumor necrosis factor-alpha level and the efficacy of infliximab for refractory pouchitis after restorative proctocolectomy in patients with ulcerative colitis

Journal of the Anus Rectum and Colon ◽

10.23922/jarc.2016-008 ◽

2017 ◽

Vol 1 (4) ◽

pp. 106-111

Author(s):

Motoi Uchino ◽

Hiroki Ikeuchi ◽

Toshihiro Bando ◽

Akihiro Hirata ◽

Teruhiro Chohno ◽

...

Keyword(s):

Ulcerative Colitis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Restorative Proctocolectomy ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Alpha Level ◽

Factor Alpha ◽

Necrosis Factor ◽

Serum Tumor Necrosis

Download Full-text

MANIPULATION OF ENDOGENOUS ADENOSINE MODULATES SERUM TUMOR NECROSIS FACTOR-ALPHA (TNF-α) DURING SEPSIS IN RATS

Shock ◽

10.1097/00024382-199906001-00088 ◽

1999 ◽

Vol 11 (Supplement) ◽

pp. 25

Author(s):

A D Sam ◽

H. Barcino ◽

A C Sharma ◽

H B Bosmann ◽

J L Ferguson ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Endogenous Adenosine ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor ◽

Serum Tumor Necrosis

Download Full-text

Severe imported malaria in a Serbian referral center

Vojnosanitetski pregled ◽

10.2298/vsp170509124p ◽

2019 ◽

Vol 76 (5) ◽

pp. 470-475

Author(s):

Jasmina Poluga ◽

Uros Karic ◽

Zorica Dakic ◽

Natasa Katanic ◽

Lidija Lavadinovic ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Severe Malaria ◽

Disease Severity ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

World Health ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor ◽

Serum Tumor Necrosis

Background/Aim. The World Health Organization estimates that 3.2 billion people are at a risk of being infected with malaria. Thus, the adequate diagnostic protocols for malaria, especially those aimed at determining disease severity, are paramount both in endemic and non-endemic setting. The aim of this study was to identify the demographic, parositological, clinical and laboratory characteristics associated with severe malaria in a non-endemic settings. Methods. We analyzed 22 patients with severe malaria and compared their clinical and laboratory findings with those of the patients with non-severe malaria in a search of predictors of disease severity. All patients were treated at the Infectious and Tropical Diseases University Hospital, Clinical Centre of Serbia in Belgrade, Serbia from 2000 to 2010. Results. The average age of patients with with severe malaria was 44.86 ? 12.33 years and men predominated (95.45%). The patients with severe malaria were infected Plasmodium falciparum (P. falciparum) significantly more frequently compared with those with non-severe disease (p =0.047). Jaundice was the most commonly observed feature of severe malaria, followed by anemia and renal failure. The multifactor analysis of variance showed that thrombocytopenia (p = 0.05) and high serum tumor necrosis factor-alpha levels (p = 0.02) were significantly associated with the disease severity. Conclusion. A high index of suspicion for malaria should be maintained when evaluating febrile patients returning from the malaria endemic regions. The elevated serum tumor necrosis factor-alpha levels and thrombocytopenia are associated with severe malaria in non-endemic settings.

Download Full-text

Cross-linking of CD4 molecules upregulates Fas antigen expression in lymphocytes by inducing interferon-gamma and tumor necrosis factor- alpha secretion

Blood ◽

10.1182/blood.v84.8.2622.2622 ◽

1994 ◽

Vol 84 (8) ◽

pp. 2622-2631 ◽

Cited By ~ 162

Author(s):

N Oyaizu ◽

TW McCloskey ◽

S Than ◽

R Hu ◽

VS Kalyanaraman ◽

...

Keyword(s):

T Cell ◽

Cell Apoptosis ◽

Tumor Necrosis ◽

Tnf Alpha ◽

Cross Linking ◽

Necrosis Factor Alpha ◽

Ifn Gamma ◽

T Cell Apoptosis ◽

Factor Alpha ◽

Necrosis Factor

Abstract We have recently shown that, in unfractioned peripheral blood mononuclear cells (PBMCs), the cross-linking of CD4 molecules (CD4XL) is sufficient to induce T-cell apoptosis. However, the underlying mechanism for the CD4XL-mediated T-cell apoptosis is largely unknown. Several recent studies have shown that Fas antigen (Ag), a cell-surface molecule, mediates apoptosis-triggering signals. We show here that cross-linking of CD4 molecules, induced either by anti-CD4 monoclonal antibody (MoAb) Leu3a or by human immunodeficiency virus-1 (HIV-1) envelope protein gp160, upregulates Fas Ag expression as well as Fas mRNA in normal lymphocytes. Addition of the tyrosine protein kinase inhibitor genistein or of the immunosuppressive agent cyclosporin A abrogated these effects. The upregulation of Fas Ag closely correlated with apoptotic cell death, as determined by flow cytometry. In addition, CD4XL resulted in the induction of interferon-gamma (IFN- gamma) and tumor necrosis factor-alpha (TNF-alpha) in the absence of interleukin-2 (IL-2) and IL-4 secretion in PBMCs. Both INF-gamma and TNF-alpha were found to contribute to Fas Ag upregulation and both anti- IFN-gamma and anti-TNF-alpha antibodies blocked CD4XL-induced Fas Ag upregulation and lymphocyte apoptosis. These findings strongly suggest that aberrant cytokine secretion induced by CD4XL and consequent upregulation of Fas Ag expression might play a critical role in triggering peripheral T-cell apoptosis and thereby contribute to HIV disease pathogenesis.

Download Full-text

Targeting Mycobacterium tuberculosis Tumor Necrosis Factor Alpha-Downregulating Genes for the Development of Antituberculous Vaccines

mBio ◽

10.1128/mbio.01023-15 ◽

2016 ◽

Vol 7 (3) ◽

Cited By ~ 19

Author(s):

Aaron Olsen ◽

Yong Chen ◽

Qingzhou Ji ◽

Guofeng Zhu ◽

Aruna Dharshan De Silva ◽

...

Keyword(s):

T Cell ◽

Tumor Necrosis Factor ◽

Host Cell ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Cell Responses ◽

Cell Immunity ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF) plays a critical role in the control of Mycobacterium tuberculosis , in part by augmenting T cell responses through promoting macrophage phagolysosomal fusion (thereby optimizing CD4 + T cell immunity by enhancing antigen presentation) and apoptosis (a process that can lead to cross-priming of CD8 + T cells). M. tuberculosis can evade antituberculosis (anti-TB) immunity by inhibiting host cell TNF production via expression of specific mycobacterial components. We hypothesized that M. tuberculosis mutants with an increased capacity to induce host cell TNF production (TNF-enhancing mutants) and thus with enhanced immunogenicity can be useful for vaccine development. To identify mycobacterial genes that regulate host cell TNF production, we used a TNF reporter macrophage clone to screen an H37Rv M. tuberculosis cosmid library constructed in M. smegmatis . The screen has identified a set of TNF-downregulating mycobacterial genes that, when deleted in H37Rv, generate TNF-enhancing mutants. Analysis of mutants disrupted for a subset of TNF-downregulating genes, annotated to code for triacylglycerol synthases and fatty acyl-coenzyme A (acyl-CoA) synthetase, enzymes that concern lipid biosynthesis and metabolism, has revealed that these strains can promote macrophage phagolysosomal fusion and apoptosis better than wild-type (WT) bacilli. Immunization of mice with the TNF-enhancing M. tuberculosis mutants elicits CD4 + and CD8 + T cell responses that are superior to those engendered by WT H37Rv. The results suggest that TNF-upregulating M. tuberculosis genes can be targeted to enhance the immunogenicity of mycobacterial strains that can serve as the substrates for the development of novel anti-TB vaccines. IMPORTANCE One way to control tuberculosis (TB), which remains a major global public health burden, is by immunization with an effective vaccine. The efficacy of Mycobacterium bovis BCG, the only currently approved TB vaccine, is inconsistent. Tumor necrosis factor alpha (TNF) is a cytokine that plays an important role in controlling TB. M. tuberculosis , the causative agent of TB, can counter this TNF-based defense by decreasing host cell TNF production. This study identified M. tuberculosis genes that can mediate inhibition of TNF production by macrophage (an immune cell critical to the control of TB). We have knocked out a number of these genes to generate M. tuberculosis mutants that can enhance macrophage TNF production. Immunization with these mutants in mice triggered a T cell response stronger than that elicited by the parental bacillus. Since T cell immunity is pivotal in controlling M. tuberculosis , the TNF-enhancing mutants can be used to develop novel TB vaccines.

Download Full-text