Terminal tracheal cells of Drosophila are immune privileged to maintain their Foxo-dependent structural plasticity

Respiratory organs fulfill several tasks, of which gas exchange is the most important. This function is also true for the Drosophila respiratory organ, the tracheal system, in which the tracheal terminal cells (TTCs), the functional equivalents of the mammalian lung’s alveoli, are the structures where gas exchange occurs. To cope with the plethora of inhaled bacteria, fungi, and viruses, the trachea, like all airway organs, developed a sophisticated innate immune system to protect its large surface area. Bacterial infection of the Drosophila larval tracheal system induced a robust immune response throughout the entire airway epithelium, except for the TTCs that lacked this response. TTCs do not express the membrane-associated peptidoglycan recognition receptor PGRP-LC, which we assume protects these susceptible cells from Immune deficiency (Imd) pathway activation and JNK- mediated cell death. Thus, TTCs can be considered an immune-privileged cell type compared to the rest of the tracheal tissue. Targeted overexpression of PGRP-LCx in these cells led to a significant reduction in branching, cell damage, and ultimately cell death, which depletion of AP-1 or foxo could rescue. We hypothesize that the structural plasticity of TTCs in response to nutritional cues and hypoxia is incompatible with a potent immune function. Both reactions, the structural plasticity, and the immune response, require the transcription factor foxo, and we showed that it is essential for structural plasticity. Thus, the immune-privileged status of TTCs is (presumably) a mechanism that ensures normal TTC function.