The Airway Antigen Sampling System: Respiratory M Cells as an Alternative Gateway for Inhaled Antigens

Abstract

In this study, we demonstrated a new airway Ag sampling site by analyzing tissue sections of the murine nasal passages. We revealed the presence of respiratory M cells, which had the ability to take up OVA and recombinant Salmonella typhimurium expressing GFP, in the turbinates covered with single-layer epithelium. These M cells were also capable of taking up respiratory pathogen group A Streptococcus after nasal challenge. Inhibitor of DNA binding/differentiation 2 (Id2)-deficient mice, which are deficient in lymphoid tissues, including nasopharynx-associated lymphoid tissue, had a similar frequency of M cell clusters in their nasal epithelia to that of their littermates, Id2+/− mice. The titers of Ag-specific Abs were as high in Id2−/− mice as in Id2+/− mice after nasal immunization with recombinant Salmonella-ToxC or group A Streptococcus, indicating that respiratory M cells were capable of sampling inhaled bacterial Ag to initiate an Ag-specific immune response. Taken together, these findings suggest that respiratory M cells act as a nasopharynx-associated lymphoid tissue-independent alternative gateway for Ag sampling and subsequent induction of Ag-specific immune responses in the upper respiratory tract.

M Cells

“…Although these NALT M cells resemble Peyer's patch M cells in their basic morphology and antigen sampling properties, it is not yet known to what extent they express the same specific markers that are characteristically expressed by Peyer's patch M cells and whether their differentiation from epithelial stem cells is regulated in a similar manner. In addition to the M cells associated with the FAE above the NALT, the upper respiratory tract of mice also includes an additional class of NALT-independent respiratory M cells positioned within the respiratory epithelium away from any lymphoid aggregates (Kim et al, 2011).…”

RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT)

“…The morphology, topographical proximity to intraepithelial lymphocytes, and ability of M cells of NALT to take up luminal antigens are similar to those of intestinal M cells (Gebert et al 1999). Histochemically, the M cells of NALT have been identified by the expression of cytokeratin 8, 18, 20, and vimentin in the rabbit palatine tonsil (Carapelli et al 2004;Gebert et al 1995;Jepson et al 1992); the expression of clusterin and class II "-tubulin in the human Waldeyer's ring (Lee et al 2010;Verbrugghe et al 2008); and 5 affinity to Ulex europaeus agglutinin I (UEA-I) lectin in murine and rat NALT (Jeong et al 1999; Kim et al 2011). Recent studies identified various unique molecules expressed in the M cells of Peyer's patches.…”

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

“…Administration of TLR2 or TLR4 ligands into the lower airways carries the potential danger of exacerbating lower airway inflammation by promoting monocytic/neutrophilic inflammation (22). Alternatively, the nasal mucosa is populated by lymphoid tissues (23), as well as the recently described M cells (24), which can serve as effective inductive sites for immune responses, while minimizing exposure of the lower airways to TLR ligands. Thus, we assessed the immunomodulatory potential of nasal application of Protollin as an adjuvant in intranasal immunotherapy of lower airway disease, in a murine model of birch pollen allergic asthma, and focused on the changes in CD4 + T cell responses induced by Protollin in vivo via the nasal mucosa.…”