Presentation Details
| Temporal Roles of Olfactory Macrophages in Host Defense in the Olfactory Epithelium Brianna M Ramirez1, Jiaying Liu1, Hongwei Liu1, Yunlu Sun2, Yaejim Kim1, Lark L Coffey1, Qizhi Gong1. 1University of California, Davis, Davis, CA.2Southern University of Science and Technology, Shenzhen, China |
Abstract
The olfactory mucosa (OM) is uniquely vulnerable because olfactory sensory neurons remain directly exposed to the environment, increasing susceptibility to pathogens. Macrophages serve as critical first-line defenders by maintaining tissue homeostasis, surveying the local environment, and defending against pathogens. Although OM macrophages have been characterized, their responses to viral infection, particularly SARS-CoV-2 (CoV2), remain poorly understood. Here, we characterized OM macrophage diversity using single-cell RNA sequencing. In addition to phagocytic and antigen-presenting populations, we identified a novel macrophage subset marked by Cd163 and Mrc1 (CD206) expression. At homeostasis, macrophages localize to the basal layer and lamina propria. With CoV2 infection, macrophages infiltrated infected regions and upregulated inflammatory cytokines and antiviral genes by 2 days post-infection (DPI). By 6 DPI, infiltration extended beyond the initial infection site, with reduced antiviral gene expression and sustained upregulation of pathways associated with antigen presentation, neuronal remodeling, phagocytosis, and neurogenesis. During acute CoV2 infection, two monocyte populations were recruited to the OM. To determine whether infiltrating monocytes give rise to resident macrophages, we employed lineage tracing using CCR2-CreER; Rosa-LSL-tdTomato mice. With acute LPS exposure, monocyte infiltration was robust but returns to baseline by 8 weeks. During CoV2 infection, monocytic lineage cells did not contribute to the immediate macrophage population at 2 DPI; however, by 6 DPI, their presence was widespread throughout the OM. Together, these findings show that OM macrophages respond to CoV2 infection and suggest roles in host defense, tissue remodeling, and olfactory dysfunction.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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