Chronic Ethanol Consumption Decreases Murine Langerhans Cell Numbers and Delays Migration of Langerhans Cells as Well as Dermal Dendritic Cells

Autor: Robert T. Cook, Kristin J. Ness, Werner W. Wilke, Ruth A. Coleman, Annette J. Schlueter, Ji Fan
Rok vydání: 2008
Předmět:
Zdroj: Alcoholism: Clinical and Experimental Research. 32:657-668
ISSN: 1530-0277
0145-6008
Popis: Alcohol is the most frequently abused substance in the United States. Alcoholism is associated with increased incidence and severity of bacterial infections (Cook, 1998; Happel and Nelson, 2005; MacGregor and Louria, 1997; Szabo, 1999). Alcoholics also appear to suffer from more skin infections than nonalcoholics (Harnisch et al., 1989; Smith and Fenske, 2000). However, the mechanism behind the observed increased susceptibility to infection is not well understood. The skin plays an important role in the defense against infection. Its responsibility is not only to restrict the entry of pathogens into the body but also to alert the innate and adaptive immune systems when this barrier is breached. To do this, the skin contains a surveillance network of specialized cells, dendritic cells (DC). The DC of the epidermis are termed Langerhans cells (LC). Murine LC can be identified as CD11c+, MHC Cl II+, Langerin+, CD8− (Douillard et al., 2005; Valladeau and Saeland, 2005). Dermal DC (dDC) represent a more heterogeneous DC population present in the dermis, and can be characterized as CD11c+, MHC Cl II+, Langerin−, CD8− (Ruedl et al., 2000). LC and dDC internalize and process antigen (Ag) encountered within the skin and simultaneously survey the epidermis for danger signals in the form of Toll-like receptor ligands or inflammatory cytokines. Upon encounter with danger signals, LC and dDC change their chemokine receptor and adhesion molecule profiles to exit the skin via the dermal lymphatics and enter the draining lymph nodes (LN). Because of their proximity to dermal lymphatics, dDC have a shorter transit time to LN than LC (Kissenpfennig et al., 2005). LC and dDC migration into the LN is a rate-limiting step in the activation of naive T cells (Gunn et al., 1999; Itano and Jenkins, 2003). It is critical that these processes not be delayed or diminished to ensure timely activation of immune responses. The effect of chronic EtOH consumption on LC and dDC migratory function has not been previously investigated. The goal of this study was to determine the effects of chronic EtOH consumption on LC and dDC migratory function using an in vivo mouse model for alcoholism (Song et al., 2002). When numbers of LC and dDC were examined in skin prior to stimulation, EtOH-fed mice demonstrated reduced LC (but not dDC), an effect that appeared to be intrinsic to the skin environment rather than the LC precursor. Net LC loss from the epidermis in response to inflammation was diminished compared to water-fed controls, and both LC and dDC from EtOH-fed mice exhibited delayed arrival in the LN compared to cells from control mice. The data presented herein indicate that EtOH-induced decreases in baseline LC numbers, as well as delays LC and dDC migratory function, may provide novel means by which EtOH-exposed DC are less able to rapidly initiate immune responses to pathological insults introduced through the skin.
Databáze: OpenAIRE
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