Nociceptor sensory neurons augment antifungal immunity during lethal Aspergillus fumigatus pneumonia 4010

Description Immunocompromised individuals are more likely to acquire Invasive Pulmonary Aspergillosis (IPA) and lethal pneumonia caused by Aspergillus fumigatus. These lead to dysregulated inflammation, altered immune responses, and airway barrier destruction. IPA treatments fail to provide absolute protection and come with substantial clinical limitations. Nociceptor sensory neurons innervate the bronchioles and airways and aid homeostasis and immune cell functions. However, the role of lung-innervating nociceptors during lethal A. fumigatus pneumonia is unknown. Here, we found that nociceptor sensory neuron ablation in mice led to a reduced survival outcome after lethal A. fumigatus pneumonia. Post-infection bronchoalveolar lavage analysis demonstrated increased fungal clearance, higher inflammatory cytokine levels, and immune cell recruitment in these mice. However, they experienced exaggerated inflammation and lung damage that led to fungal dissemination and reduced survival. Furthermore, we found that the neuropeptide calcitonin gene-related peptide (CGRP) increases the phagocytosis and killing capacity of neutrophils, monocytes, and macrophages after coincubation with A. fumigatus. Altogether, our data show that nociceptor neurons and their secreted CGRP regulate the extent of collateral inflammation and lung damage that occurs during A. fumigatus pneumonia. Our results suggest that the nociceptor-immune crosstalk is a potential therapeutic target for the treatment of IPA. Funding Sources This work was supported by funding from NIH, K-INBRE, the American Lung Association, and the Johnson Cancer Research Center (JCRC). Topic Categories Neuroimmunology (NEUR)