Short palate, lung, and nasal epithelial clone-1 (SPLUNC1) is a protein abundantly expressed by the respiratory epithelium of the proximal lower respiratory tract, a site of great environmental exposure. Previous studies showed that SPLUNC1 exerts antimicrobial effects, regulates airway surface liquid and mucociliary clearance, and suppresses allergic airway inflammation. We studied SPLUNC1 to gain insights into its role in host defense. In the lower respiratory tract, concentrations of SPLUNC1 are high under basal conditions. In models of pneumonia caused by common respiratory pathogens, and in Th1-induced and Th2-induced airway inflammation, SPLUNC1 secretion is markedly reduced. Pathogen-associated molecular patterns and IFN-g act directly on airway epithelial cells to inhibit SPLUNC1 mRNA expression. Thus, SPLUNC1 is quickly suppressed during infection, in response to an insult on the epithelial surface. These experiments highlight the finely tuned fluctuations of SPLUNC1 in response to exposures in the respiratory tract, and suggest that the loss of SPLUNC1 is a crucial feature of host defense across airbreathing animal species.Keywords: SPLUNC1; inflammation; innate; immunity; mucosaThe respiratory tract continuously interacts with environmental irritants and pathogens. These stimuli constitute part of an intricate network of signals that activate host defenses. Airway epithelial cells participate actively in this process by producing antimicrobial and immune mediators that maintain homeostasis during steady-state conditions, and promote inflammation during injury.The palate, lung, and nasal epithelial clone (PLUNC) genes are members of the bactericidal permeability-increasing protein foldcontaining (BPIF)/PLUNC protein family (1, 2). These genes are focally expressed by epithelial cells throughout the respiratory tracts of multiple air-breathing vertebrates (3). In total, 11 human genes and 14 murine genes have been described to date, located within a single locus on chromosome 20 and chromosome 2, respectively (4, 5). These genes code for the PLUNC proteins, which are classified into six short and eight long PLUNCs, based on their lengths.Short PLUNC 1 (SPLUNC1) is a 25-kD protein secreted by epithelial cells in the upper airway and proximal lower respiratory tract (3, 6-10). SPLUNC1 is readily detected in human saliva and in nasal and bronchial epithelial washings at concentrations ranging from 34.7 ng/ml to 13.8 mg/ml (6, 10-12). In tracheal epithelial-cell supernatants SPLUNC1 constituted 10% of the total soluble protein, making it one of the most highly expressed proteins produced by airway epithelial cells (7).SPLUNC1 shares structural similarities with the immunomodulatory proteins bactericidal permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (4, 13-15). It was initially hypothesized to express antimicrobial functions, and has been shown to inhibit the growth of multiple pathogens (16-19), inhibit biofilm formation, and possess surfactant properties (20,21). Although mos...
HIV remains one of the most important deadly infections today, due to the lack of a preventive vaccine and limited access to medical care in developing countries. In developed countries antiretroviral therapy is available but the regime is unable to eliminate the virus, implying that life-long therapy is necessary. Dendritic cells (DCs) are important mediators of cellular and humoral immune responses and hence offer a promising therapeutic vaccination strategy to attenuate disease progression. The current knowledge in DC subsets and their functional plasticity are prominent determinants in harnessing the full immunostimulatory potential of dendritic cells. Type of antigen, immunogen delivery method, optimal interaction of antigenic peptide and T cells, and avoidance of tolerogenic responses are some of the elements that need to be considered to develop an efficient immunotherapy. Novel strategies that modulate DC functions that eventually trigger a robust cellular response against a broad T cell repertoire are needed. This review focuses on current DC-based vaccine strategies for optimal induction of immune responses.
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