Anatomical Location Determines the Distribution and Function of Dendritic Cells and Other APCs in the Respiratory Tract

Abstract

APCs, including dendritic cells (DC), are central to Ag surveillance in the respiratory tract (RT). Research in this area is dominated by mouse studies on purportedly representative RT-APC populations derived from whole-lung digests, comprising mainly parenchymal tissue. Our recent rat studies identified major functional differences between DC populations from airway mucosal vs parenchymal tissue, thus seriously questioning the validity of this approach. We addressed this issue for the first time in the mouse by separately characterizing RT-APC populations from these two different RT compartments. CD11chigh myeloid DC (mDC) and B cells were common to both locations, whereas a short-lived CD11cneg mDC was unique to airway mucosa and long-lived CD11chigh macrophage and rapid-turnover multipotential precursor populations were predominantly confined to the lung parenchyma. Airway mucosal mDC were more endocytic and presented peptide to naive CD4+ T cells more efficiently than their lung counterparts. However, mDC from neither site could present whole protein without further maturation in vitro, or following trafficking to lymph nodes in vivo, indicating a novel mechanism whereby RT-DC function is regulated at the level of protein processing but not peptide loading for naive T cell activation.

Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination

“…S1A, Left). By gating on Alexa 647 + , CD45 + lung cells, we found that, 24 h after delivery, the majority of cells involved in NP uptake (80% of Alexa 647 + cells) were a subset of CD11c + , F4/80 + , CD11b low , MHC-II low , highly autofluorescent macrophages that have previously been shown to reside in the lung parenchyma (19,20). The remaining proportion (20% of Alexa 647 + cells) consisted of CD11c + , MHC-II high DCs (Fig.…”

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).…”

“…Two main subsets of murine RTDC have been identified -myeloid DC (Lambrecht et al, 2000a,b) and plasmacytoid DC (de Heer et al, 2004), with further subsets evident dependant on anatomical location (von Garnier et al, 2005).…”

“…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).…”

Induction of respiratory immune responses in the chicken; implications for development of mucosal avian influenza virus vaccines

“…In alveolar space, a population of alveolar MPh is also present. In the RT, tracheal DC have a rapid turnover rate (2-3 days), while interstitial DC are long lived (Holt et al 1994;von Garnier et al 2005).…”