In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens

Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections. Here, we report a novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo. We show that in vivo DC are required to cross-prime CTL precursors. Our results thus define a unique in vivo role of DC, i.e., the sensitization of the immune system for cell-associated antigens. DC-depleted mice fail to mount CTL responses to infection with the intracellular bacterium Listeria monocytogenes and the rodent malaria parasite Plasmodium yoelii.     

Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN

Here, we describe the isolation and characterization of the rhesus macaque homolog for human DC-SIGN, a dendritic cell-specific C-type lectin. mac-DC-SIGN is 92% identical to hu-DC-SIGN. mac-DC-SIGN preserves the virus transmission function of hu-DC-SIGN, capturing and efficiently transducing simian and human immunodeficiency virus to target CD4(+) T cells. Surprisingly, however, mac-DC-SIGN plays no discernable role in the ability of rhesus macaque dendritic cells to capture and transmit primate lentiviruses. Expression and neutralization analyses suggest that this process is DC-SIGN independent in macaque, although the participation of other lectin molecules cannot be ruled out. The ability of primate lentiviruses to effectively use human and rhesus dendritic cells in virus transmission without the cells becoming directly infected suggests that these viruses have taken advantage of a conserved dendritic cell mechanism in which DC-SIGN family molecules are significant contributors but not the only participants.     

Resistance of primary murine CD4+ T cells to Helicobacter pylori vacuolating cytotoxin

Persistent colonization of the human stomach by Helicobacter pylori is a risk factor for the development of gastric cancer and peptic ulcer disease. H. pylori secretes a toxin, VacA, that targets human gastric epithelial cells and T lymphocytes and enhances the ability of H. pylori to colonize the stomach in a mouse model. To examine how VacA contributes to H. pylori colonization of the mouse stomach, we investigated whether murine T lymphocytes were susceptible to VacA activity. VacA inhibited interleukin-2 (IL-2) production by a murine T-cell line (LBRM-33), similar to its effects on a human T-cell line (Jurkat), but did not inhibit IL-2 production by primary murine splenocytes or CD4+ T cells. VacA inhibited activation-induced proliferation of primary human CD4+ T cells but did not inhibit the proliferation of primary murine CD4+ T cells. Flow cytometry studies indicated that the levels of VacA binding to primary murine CD4+ T cells were significantly lower than levels of VacA binding to human CD4+ T cells. This suggests that the resistance of primary murine CD4+ T cells to VacA is attributable, at least in part, to impaired VacA binding to these cells.     

CD1d-restricted human natural killer T cells are highly susceptible to human immunodeficiency virus 1 infection

Human natural killer (NK) T cells are unique T lymphocytes that express an invariant T cell receptor (TCR) Valpha24-Vbeta11 and have been implicated to play a role in various diseases. A subset of NKT cells express CD4 and hence are potential targets for human immunodeficiency virus (HIV)-1 infection. We demonstrate that both resting and activated human Valpha24(+) T cells express high levels of the HIV-1 coreceptors CCR5 and Bonzo (CXCR6), but low levels of CCR7, as compared with conventional T cells. Remarkably NKT cells activated with alpha-galactosylceramide (alpha-GalCer)-pulsed dendritic cells were profoundly more susceptible to infection with R5-tropic, but not X4-tropic, strains of HIV-1, compared with conventional CD4(+) T cells. Furthermore, resting CD4(+) NKT cells were also more susceptible to infection. After initial infection, HIV-1 rapidly replicated and depleted the CD4(+) subset of NKT cells. In addition, peripheral blood NKT cells were markedly and selectively depleted in HIV-1 infected individuals. Although the mechanisms of this decline are not clear, low numbers or absence of NKT cells may affect the course of HIV-1 infection. Taken together, our findings indicate that CD4(+) NKT cells are directly targeted by HIV-1 and may have a potential role during viral transmission and spread in vivo.     

The innate immune system and HIV pathogenesis

Innate immunity represents the first line of defense against microbial infections. The innate immune system is activated by conserved structures present on most pathogens and profoundly regulates subsequent adaptive immune responses. HIV is notorious for evading and disrupting the immune system. Although HIV directly targets and gradually destroys the adaptive immunity, it has become clear that the virus also perturbs the components of the innate immune system. In this paper, we review the role of two innate lymphocyte subsets, natural killer and natural killer T cells, that are disrupted during HIV infection.     

Determination of the etiological organism during acute exacerbations of COPD and efficacy of azithromycin, ampicillin-sulbactam, ciprofloxacin and cefaclor. Turkish Thoracic Society COPD Working Group.

Acute exacerbations, most of which are due to lower respiratory tract infections, cause great morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD) and most of these are due to lower respiratory tract infections. The aim of this study was to determine the causative organism and the effects of azithromycin, ampicillin sulbactam (sultamicillin), ciprofloxacin and cefaclor monohydrate therapy in COPD. One hundred and six patients with COPD in acute exacerbation were randomized into four groups for empiric antibiotic treatment following lung function tests and sputum examination. The most common strains isolated from sputum were Haemophilus influenzae (30.8%), Streptoccocus pneumoniae (12%) and Moraxella catarrhalis (7.7%). Azithromycin, sultamicillin, ciprofloxacin and cefaclor monohydrate were found to be effective in treating COPD exacerbations.