NALT M cells are important for immune induction for the common mucosal immune system

Abstract

Nasopharynx-associated lymphoid tissue (NALT) is one of the major constituents of the mucosa-associated lymphoid tissue (MALT), and has the ability to induce antigen-specific immune responses. However, the molecular mechanisms responsible for antigen uptake from the nasal cavity into the NALT remain largely unknown. Immunohistochemical analysis showed that CCL9 and CCL20 were co-localized with glycoprotein 2 (GP2) in the epithelium covering NALT, suggesting the existence of M cells in NALT. In analogy with the reduced number of Peyer's patch M cells in CCR6-deficient mice, the number of NALT M cells was drastically decreased in CCR6-deficient mice compared with the wild-type mice. Translocation of nasally administered Salmonella enterica serovar Typhimurium into NALT via NALT M cells was impaired in CCR6-deficient mice, whereas S. Typhimurium demonstrated consistent co-localization with NALT M cells in wild-type mice. When wild-type mice were nasally administered with an attenuated vaccine strain of S. Typhimurium, the mice were protected from a subsequent challenge with wild-type S. Typhimurium. Antigen-specific fecal and nasal IgA was detected after nasal immunization with the attenuated vaccine strain of S. Typhimurium only in wild-type mice but not in CCR6-deficient mice. Taken together, these observations demonstrate that NALT M cells are important as a first line of defense against infection by enabling activation of the common mucosal immune system (CMIS).

Anatomical Uniqueness of the Mucosal Immune System (GALT, NALT, iBALT) for the Induction and Regulation of Mucosal Immunity and Tolerance

“…Similar to MALT in the gut, NALT has a dome epithelium that expresses the chemokines CCL20 and CCL9 [181,182]. However, unlike Peyer's patches, it does not express CXCL16 [123].…”

“…CCR6-expressing DCs and B cells fill the dome region under the epithelium and are closely associated with M cells [185]. As in Peyer's patches, interactions between CCR6-expressing leukocytes and M cells are important for the maintenance of NALT structure and function [182].…”

“…Interactions with lymphocytes are also an important part of M cell maturation in NALT, as the morphology of M cells and the basolateral pocket are lost when lymphocytes are depleted [198]. The interactions between leukocytes and M cells utilizes CCR6 [182,185], as the number of M cells is reduced in the NALT of CCR6-deficient mice. Moreover, the antigentransporting ability of the M cells remaining in CCR6-deficient mice is also impaired [182], leading to poor IgA responses to nasally administered antigens.…”

“…The interactions between leukocytes and M cells utilizes CCR6 [182,185], as the number of M cells is reduced in the NALT of CCR6-deficient mice. Moreover, the antigentransporting ability of the M cells remaining in CCR6-deficient mice is also impaired [182], leading to poor IgA responses to nasally administered antigens. Although interactions with B cells are not required for the initial development of M cells, B cells trigger the TNFR family member CD137 (commonly known as 4-1BB) on M cells by its ligand on B cells [50], which maintains M cell morphology, promotes the formation of the basolateral pocket, and facilitates their ability to transport antigens and particulates [50].…”

Current and New Approaches for Mucosal Vaccine Delivery

“…The nasal cavity is equipped with nasopharyngeal-associated lymphoid tissue (NALT), which is highly similar to Peyer's patches in the ileum [174]. NALT is also covered with M cells that have active antigen sampling capacity [175]. Intraepithelial DCs project dendrites toward mucosal lumen and sample antigens.…”