ALVEOLAR MACROPHAGE EXPRESSED NKR-P1B INTERACTS WITH CLR-G ON TYPE-II PNEUMOCYTES TO MODULATE ALVEOLAR MACROPHAGE LIPID METABOLISM AND SURVIVAL

Abstract

Alveolar macrophages (AMs) are specialized, tissue-resident macrophages at the frontline of pulmonary defense against inhaled pathogens, and surfactant homeostasis. To perform these roles, AMs undergo cellular programming in response to tissue- and cell-specific signals elicited by the pulmonary niche. However, the tissue-specific mechanisms that guide AMs metabolism have remained elusive. We show that the natural killer (NK) cell-associated receptor, NKR-P1B, expressed on AMs plays a critical role in inducing AM metabolic programming. Nkrp1b-/- mice exhibit significant vulnerability to pneumococcal infections due to an age-dependent collapse in their AMs population. AMs derived from Nkrp1b-/- mice show abnormal rates of surfactant lipid uptake and dysregulated surfactant metabolism. We also find that an interaction between AMs expressed NKR-P1B, and type-II pneumocyte expressed Clr-g, provides a critical link required to induce and fine tune AMs metabolic profile, thus outlining the first example of a tissue-specific, receptor-ligand interaction acting as a determinant of AMs metabolism.