Co-localization of lymphoid aggregates and lymphatic networks in nose- (NALT) and lacrimal duct-associated lymphoid tissue (LDALT) of mice

Abstract

BackgroundThe lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the association of head lymphoid tissues with the lymphatics has remained unknown although the mouse is the most often used species in immunology.ResultsHere, we studied the association of nasal and nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month-old mice. We performed paraffin sectioning of whole, decalcified heads, and immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and Podoplanin. Most parts of the nasal mucous membrane do not contain any lymphatics. Only the region of the inferior turbinates contains lymphatic networks, which are connected to those of the palatine. Nose-associated lymphoid tissue (NALT) is restricted to the basal parts of the nose, which contain lymphatics. NALT is continued occipitally and can be found at both sides along the sphenoidal sinus, again in close association with lymphatic networks. Nasal lymphatics are connected to those of the ocular region via a lymphatic network along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated lymphoid tissue (LDALT) has a dense supply with lymphatics.ConclusionsNALT and LDALT play a key role in the immune system of the mouse head, where they function as primary recognition sites for antigens. Using the dense lymphatic networks along the NLD described in this study, these antigens reach lymphatics near the palatine and are further drained to lymph nodes of the head and neck region.NALT and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we suggest a causative connection of lymphatic vessels and the development of lymphoid tissues.

Mucosa-Associated Lymphoid Tissue and Tertiary Lymphoid Structures of the Eye and Ear in Laboratory Animals

“…Examination of MALT in the lacrimal drainage system (except the lacrimal puncta and NLDO) and ear is challenging due to the need for blind collection in a bony vault. The LDALT acts as a conduit for immune interactions between the NALT and the eye, 11,31,32 and collection of 1 or more of the lacrimal gland, CALT with lacrimal puncta, lacrimal canaliculi, lacrimal sac, NLD, NLDO, NALT or NPT, and regional draining lymph nodes (parotid, retropharyngeal, and mandibular) should be considered to fully evaluate the response of the eye to therapeutics, vaccines, and medical devices. The most likely site of MALT in the ear is in the cartilaginous portion of the eustachian tube near the oropharynx, but responses in this eustachian MALT may also reflect changes in the oropharynx or the middle ear, rather than just a response within the eustachian tube.…”

“…29 Nasal-associated lymphoid tissue and the ocular immune system are interconnected by the lacrimal system. 6,9,17,30,31 An abundance of lymphatics in the NALT and around the NLDO in the nasal cavity of mice appears to connect the immune responses of the nose and eye and the regional draining lymph nodes. 11,31 Surgical occlusion at the lacrimal (conjunctival) punctum in the rabbit does not alter the conjunctival response but enhances the systemic response after local ocular immunization.…”

“…6,9,17,30,31 An abundance of lymphatics in the NALT and around the NLDO in the nasal cavity of mice appears to connect the immune responses of the nose and eye and the regional draining lymph nodes. 11,31 Surgical occlusion at the lacrimal (conjunctival) punctum in the rabbit does not alter the conjunctival response but enhances the systemic response after local ocular immunization. After intranasal immunization with lacrimal system occlusion, the ocular, but not the systemic response, was decreased.…”

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

“…NALT extends along the length of the nasal passages and consists of multiple B cell follicles arranged like a string of beads separated by interfollicular areas [175,179]. Like Peyer's patches, the interfollicular areas contain numerous T cells and DCs that are arranged on a stromal network of CCL19-expressing FRCs, whereas the B cell follicles and germinal centers are organized around stromal networks of CXCL13-expressing FDCs [175,180].…”

“…However, efferent lymphatic vessels are found at the outside edge of the interfollicular T cell areas of NALT, where they collect effector cells that were primed and expanded in NALT [180]. Interestingly, the lymphatic vasculature of NALT connects with the lymphatic vasculature draining the ocular region that contains another mucosal lymphoid tissue, the lacrimal-ductassociated lymphoid tissue (LDALT) [180,189]. Thus ocular and nasal lymphatics seem to converge on their way to downstream cervical LNs.…”