Dendritic Cells Are Recruited into the Airway Epithelium during the Inflammatory Response to a Broad Spectrum of Stimuli

Abstract

A key rate-limiting step in the adaptive immune response at peripheral challenge sites is the transmission of antigen signals to T cells in regional lymph nodes. Recent evidence suggests that specialized dendritic cells (DC) fulfill this surveillance function in the resting state, but their relatively slow turnover in most peripheral tissues brings into question their effectiveness in signaling the arrival of highly pathogenic sources of antigen which require immediate mobilization of the full range of host defenses for maintenance of homeostasis. However, the present report demonstrates that recruitment of a wave of DC into the respiratory tract mucosa is a universal feature of the acute cellular response to local challenge with bacterial, viral, and soluble protein antigens. Consistent with this finding, we also demonstrate that freshly isolated respiratory mucosal DC respond in vitro to a variety of CC chemokines as well as complementary cleavage products and N-formyl-methionyl-leucine-phenylalanine. This suggests that rapid amplification of specific antigen surveillance at peripheral challenge sites is an integral feature of the innate immune response at mucosal surfaces, and serves as an “early warning system” to alert the adaptive immune system to incoming pathogens.

The Cutaneous Response in Humans toTreponema pallidumLipoprotein Analogues Involves Cellular Elements of Both Innate and Adaptive Immunity

“…Although increased numbers of DCs have been reported in different tissue models of inflammation (41,58,69), the relative importance of recruitment from blood vs resident tissue sources has not been well established. For this reason, the source of DCs in the blister fluids is an important question.…”

“…DCs, professional APCs whose primary function is to capture and process Ags for presentation to T and B cells (39,40), can be recruited to peripheral sites by a broad range of inflammatory stimuli (41). Because of their unique function at the interface between the innate and adaptive immune responses, we next asked whether lipopeptides could recruit these potent inducer cells into skin.…”

Impact of Bronchial Epithelium on Dendritic Cell Migration and Function: Modulation by the Bacterial Motif KpOmpA

“…Recent data suggest that DC behavior is locally controlled by lung environment and particularly by bronchial epithelial cells (BEC) (9 -11). In addition to GM-CSF, these BEC produce several cytokines and chemokines and express adhesion molecules potentially involved in DC traffic, as shown after exposure to diesel exhausted particles or allergens (6,11). In both allergic patients and nonatopic subjects, allergen-exposed BEC trigger the recruitment of monocyte-derived DC (MDDC) precursors through the secretion of CCL2, CCL5, and CXCL10.…”

“…Precursor cells first migrate from the bone marrow to resident sites in tissues such as lung. At steady state, due to the environment, immature DC and/or their precursors are continuously recruited to the airway mucosa where inhaled Ags are sampled (6). Upon activation by inflammatory mediators or microbial components, they undergo a complex process of maturation allowing their migration toward the regional lymph nodes (7) through a modification of adhesion molecule and chemokine receptor expression (8).…”

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

“…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). Once in the DLN, DC have been reported to stimulate naïve T cells (Lambrecht et al, 1998;Vermaelen et al, 2001).…”