Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces.

Abstract

SummaryImmunohistochemical analysis of challenge sites such as skin and the peritoneal cavity has identified neutrophils as virtually the sole cellular participants in acute bacterial inflammation, peak influx occurring 24-48 h in advance of mononuclear cell populations associated with adaptive immunity This study challenges the general applicability of this paradigm. We demonstrate here that the earliest detectable cellular response after inhalation ofMoraxdla catarrhalis organisms is the recruitment of putative class II major histocompatibflity complex-bearing dendritic cell (DC) precursors into the airway epithelium, the initial wave arriving in advance of the neutrophil influx. Unlike the neutrophils which rapidly transit into the airway lumen, the DC precursors remain within the epithelium during the acute inflammatory response where they differentiate, and develop the dendriform morphology typical of resident DC found in the normal epithelium. During the ensuing 48-h period, these cells then migrate to the regional lymph nodes. No comparable DC response was observed after epidermal or intraperitoneal challenge, and it may be that mucosal surfaces are unique in their requirement for rapid DC responses during acute inflammation. We hypothesize that the role of the DC influx during acute inflammation may be surveiUance for opportunistic viruses, and that this covert protective mechanism is operative at a restricted number of mucosal tissue sites. p revious reports from this laboratory have established the importance of dendritic cells (DC) as APC within normal lung tissue (1, 2), and have additionally shown that a functionally and morphologically identical DC population exists within the epithelial lining of the conducting airways of both humans (3) and rodents (4, 5), where they form a contiguous network analogous to the Langerhans cell (LC) population in the epidermis.We have also recently presented evidence that the density, distribution, and surface phenotype of airway DC populations reflects the level of stimulation provided by inhalation of airborne irritant stimuli (5). Moreover, brief exposure to aerosolized bacterial LPS was demonstrated to induce a transient increase (,o50%) in the density of airway intraepithelial DC during the 24-48-h period after exposure, suggesting active participation of DC in the acute inflammatory response (5). The present study sought to further elucidate the role of DC in acute inflammation in the airways, employing a much more potent inhaled stimulus in the form of whole bacteria. Materiah and MethodsAnimals. Specific pathogen-free (SPF) adult PVG rats were used in these experiments. They were barrier housed under dust-free conditions, as detailed previously (5).Aerosol Exposure The animals were exposed for 60 rain to an aerosol of heat-killed MoraxeUa catarrhalis organisms (clinical hospital isohte) suspended in normal saline at '~109 CFU/ml.Antibodies and Iraraunostaining. The mAbs Ox6 (Ia), Ox19 (CDS; pan T cell), Ox12 (r light chains; pan B cell) (6), and Ox 42 (~ cha...

Local and Systemic Immune Responses to Intratracheal Instillation of Antigen and DNA Vaccines in Mice

“…injection of an antigen load, at which point they develop antigen-presenting-cell activities and migrate to regional lymph nodes over several days after contact with the antigen (16,17). However, these studies did not assess the involvement of remote lymphoid organs such as the spleen in the immune response.…”

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

“…In contrast to parenterally administered allergens, orally applicated allergens underlie the activity of salivary enzymes, proteases and the low pH, which as the first line mechanisms of defense inactivate most of the relevant epitopes of the allergens before they reach the APC of the mucosal tissue (66). Regarding the mucosal surfaces of the gastrointestinal tract the primary APC type at the interface to the environment are DC which are regarded as the key factors in controlling T-cell responses in the gut wall (Table 1) (67)(68)(69)(70).…”

The role of dendritic cells and regulatory T cells in the regulation of allergic asthma

“…We have shown that airway RTDC become activated and up-regulate their capacity to capture and process inhaled allergen prior to the onset of Th2-mediated airways inflammation in mice, suggesting that RTDC play an important early role in the activation and recruitment of Th2 cells to the airways (von Garnier et al, 2007). In addition to the airway epithelium, RTDC subsets are also present in the submucosa and lung parenchyma although subset distribution and turnover rates differ at these sites (Holt et al, 1994;von Garnier et al, 2005). We and others have shown that RTDC are capable of capturing inhaled allergens and rapidly transporting these to DLN for presentation to T cells and that the rate of this transport can be modified by microbial products (Vermaelen et al, 2001(Vermaelen et al, , 2003Wikstrom et al, 2006).…”

“…This DC subset has a high migratory capacity for trafficking antigen to the draining lymph nodes (Lambrecht, 2001;Vermaelen et al, 2001;von Garnier et al, 2007). CD11c+MHCIIhi DC in the respiratory mucosa are known to exhibit a high rate of turnover (approximate half-life of 12 h) as antigen-bearing DC continuously migrate to the DLN and are replaced by de novo DC from the bone marrow (Holt et al, 1994;Lambrecht et al, 1998;von Garnier et al, 2005). Although outside the scope of this review, DC migration into and from the airways is modulated by the expression of chemokine receptors (Stumbles et al, 2001;Jakubzick et al, 2006) and can be modified by microbial exposure (McWilliam et al, 1994(McWilliam et al, , 1996Stumbles et al, 2001).…”