Helicobacter pylori infection is associated with gastric epithelial damage, including apoptosis, ulceration, and cancer. Although bacterial factors and the host response are believed to contribute to gastric disease, no receptor has been identified that explains how the bacteria attach and signal the host cell to undergo apoptosis. Using H. pylori as “bait” to capture receptor proteins in solubilized membranes of gastric epithelial cells, class II major histocompatibility complex (MHC) molecules were identified as a possible receptor. Signaling through class II MHC molecules leading to the induction of apoptosis was confirmed using cross-linking IgM antibodies to surface class II MHC molecules. Moreover, binding of H. pylori and the induction of apoptosis were inhibited by antibodies recognizing class II MHC. Since type 1 T helper cells are present during infection and produce interferon (IFN)-γ, which increases class II MHC expression, gastric epithelial cell lines were exposed to H. pylori in the presence or absence of IFN-γ. IFN-γ increased the attachment of the bacteria as well as the induction of apoptosis in gastric epithelial cells. In contrast to MHC II–negative cell lines, H. pylori induced apoptosis in cells expressing class II MHC molecules constitutively or after gene transfection. These data describe a novel receptor for H. pylori and provide a mechanism by which bacteria and the host response interact in the pathogenesis of gastric epithelial cell damage.

The transcription factor nuclear factor (NF)-kB controls the expression of numerous respiratory syncytial virus (RSV)-inducible inflammatory and immunomodulatory genes. Using a BALB/c mouse model, the present article shows that RSV potently and specifically activates NF-kB in vivo, a process that involves nuclear translocation of the subunits RelA, p50, and c-Rel in the lung. By depletion of alveolar macrophages (AMs) in BALB/c mice and use of C3H/HeJ mice lacking a functional Toll-like receptor (TLR)-4 signaling pathway, we demonstrate the existence of distinct but sequentially integrated RSV-inducible early NF-kB responses in the lung. The first response occurs early after RSV inoculation, is AM and TLR4 dependent, and is viral replication independent, whereas the second response involves epithelial cells and/or inflammatory cells, is TLR4 independent, and requires viral replication. NF-kB may be considered a central activator of not only inflammatory but also innate immune responses to RSV.Respiratory syncytial virus (RSV), the major cause of serious lower respiratory tract infections in infancy and early childhood [1], can be considered among the most potent biological stimuli inducing the expression and/or secretion of proinflammatory and immunomodulatory mediators [2-4]. These events have been extensively demonstrated in airway epithelial cells, the primary site of RSV replication, and in other cell types that are targets of abortive viral replication or viral attachment only (such as monocytes/macrophages, eosinophils, and neutrophils). In vitro, RSV has been shown to induce expression of a number of genes in epithelial cells and macrophages, including the cytokines interleukin (IL)-1 [5], tumor necrosis factor (TNF)-a, IL-6 [6], and IL-10 [7]; the CXC chemokines IL-8, growth-related oncogene (GRO)-a, epithelial-derived neutrophil-activating protein(ENA)-

Lower respiratory tract disease caused by respiratory syncytial virus (RSV) is characterized by profound airway mucosa inflammation, both in infants with naturally acquired infection and in experimentally inocuRespiratory syncytial virus (RSV) is the major cause of serious lower respiratory disease in infancy and early childhood (5). Bronchiolitis, the more severe clinical manifestation of RSV infection, is characterized by necrosis and sloughing of the respiratory epithelium and plugging of the small bronchioles with fibrin and mucus. An intense peribronchial infiltration of mononuclear cells (lymphocytes and monocytes) occurs, with considerable edema (1, 8, 10). In addition, presence of the granule-associate cytotoxic proteins histamine, eosinophil cationic protein, and major basic protein in nasopharyngeal secretions and tracheobronchial aspirates suggests that RSV infection triggers the migration to the airways and activation of basophils and eosinophils (12,17,37,46). The evidence of an inverse correlation between the levels of these cytotoxic mediators and the degree of oxygen saturation in RSV-infected infants further underscores the critical role played by mucosal inflammation in the pathogenesis of RSV airway disease (12,45,46).The mouse model shows close similarity to the pathogenesis of RSV-induced lower airway disease in humans. In BALB/c mice, RSV rapidly replicates in the lungs after intranasal inoculation, and induces mononuclear cell infiltration around peribronchial and perivascular tissues (41) and objective plethysmographic signs of pulmonary dysfunction (i.e., increased respiratory rates and airway hyperresponsiveness) (29, 44).These pathophysiologic changes correlate with the amount of viral inoculum (44), consistent with the observation that more severe disease occurs in infected children who have higher concentrations of RSV in their secretions (4, 16).The mechanisms that regulate selective recruitment of inflammatory cells to the airways and their activation following RSV infection are still largely unknown. Similarly, virus-or host-specific factors that may influence these events have not been yet identified. Much of the cellular response at sites of tissue inflammation is controlled by gradients of chemotactic factors that direct leukocyte transendothelial migration and movement through the extracellular matrix. The composition of this cellular response is dependent upon the discrete target cell selectivity of these chemotactic molecules. Chemokines, a superfamily of small chemotactic cytokines, have emerged as central regulatory molecules in inflammatory, immune, and infectious processes of the lung (28). Chemokines have been primarily divided into two main subfamilies, CXC (␣) and CC (␤), upon their sequence homology and the position of the first two cysteine residues. In general, this subdivision is mirrored by the activity of these two chemokine groups on neutrophils (CXC) or monocytes, eosinophils, and basophils (CC). However, within the CXC subfamily, chemokines such as gamma inte...