Distinct olfactory mucosal macrophage populations mediate neuronal maintenance and pathogen defense

Area of Science:

• Immunology
• Neuroscience
• Olfactory Biology

Background:

• The olfactory mucosa serves dual roles in smell perception and airway/brain immune defense.
• Understanding immune cell interactions within the olfactory mucosa is crucial for addressing olfactory dysfunction.
• Macrophages are the predominant immune cells in the uninflamed olfactory mucosa.

Purpose of the Study:

• To identify and characterize distinct macrophage populations in the olfactory mucosa.
• To elucidate the functional roles of these macrophages in neuronal maintenance and immune response.
• To investigate the relevance of these findings in human olfactory biopsies and post-COVID-19 smell loss.

Main Methods:

• Transcriptional analysis of murine olfactory mucosa macrophages.
• Immunohistochemistry to identify macrophage localization and association with neurons.
• Analysis of human olfactory biopsies and correlation with smell loss severity.

Main Results:

• Two macrophage populations identified: P2ry12^hi (neuron-associated, phagocytic) and MHC Class II^hi (cytokine production, antigen presentation).
• P2ry12^hi macrophages are long-term residents, while MHC Class II^hi macrophages are rapidly replaced.
• Human olfactory biopsies show similar macrophage signatures; P2ry12-like macrophages are reduced in long-term COVID-19 smell loss patients.

Conclusions:

• Two distinct olfactory macrophage populations differentially regulate neuronal interactions and immune responses.
• These findings advance the understanding of olfactory immunity and tissue-resident macrophage biology.
• The identified macrophage populations and their alterations in disease offer potential therapeutic targets for olfactory disorders.