The respiratory tract is constantly exposed to pathogens that require
iron for proliferation and virulence. Pulmonary
iron levels are increased in several
lung diseases and associated with increased susceptibility to
infections. However, regulation of lung
iron homeostasis and its cross talk to pulmonary immune responses are largely unexplored. Here we investigated how increased lung
iron levels affect the early pulmonary inflammatory response. We induced acute local
pulmonary inflammation via aerosolized LPS in a mouse model of hereditary
hemochromatosis type 4 (Slc40a1 C326S/C326S), which is hallmarked by systemic and pulmonary
iron accumulation, specifically in alveolar macrophages. We show that Slc40a1 C326S/C326S mice display a mild attenuation in the LPS-induced pulmonary inflammatory response, with a reduced upregulation of some pro-inflammatory
cytokines and
chemokines. Despite mildly reduced
cytokine levels, there is no short-term impairment in the recruitment of neutrophils into the bronchoalveolar space. These data suggest that increased pulmonary
iron levels do not strongly alter the acute inflammatory response of the lung.