The enzyme carbonic anhydrase IV is required to regulate the bioenergetic state and antihelminth functions of alveolar macrophages
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B573
Abstract ID: 4650
Presenting Author:
John J Ponessa , Postdoctoral Fellow at Rutgers New Jersey Med. Sch.
Abstract:
Helminth infections are a global cause of economic hardship and morbidity. To combat these infections, the host initiates type 2 immune responses that serve to reduce parasitic burdens while simultaneously promoting the healing of affected tissues. Previous work by our lab and others have shown that alveolar macrophages (AMs) with an alternatively activated (M2) phenotype are critical regulators of these host protective responses. Our recent studies have also revealed that AMs express high levels of the enzyme carbonic anhydrase 4 (Car4) that is associated with their M2 activation. Despite these advances, whether Car4 regulates the M2 polarization of AMs is unknown. To test this, we generated novel Car4-floxed mice to perform lineage-specific deletion experiments. Mice with Car4-deficient AMs (Car4-AM-/-) exhibited spontaneous increases in M2- and fibrosis-associated markers. Naïve Car4-AM-/- mice also presented with lung dyslipidemia and reduced pulmonary function. Consistent with the ability of Car4 to regulate AM activation, helminth infected Car4-AM-/- mice also showed dysregulated M2 responses and increased lung pathology. RNAseq and metabolic analysis of sort-purified Car4-deficient AMs demonstrate that they exhibit an altered bioenergetic state consistent with their enhanced M2 polarization. These data suggest that Car4 dictates the activation of AMs by regulating their metabolic state, restricting their M2 activation and thereby preventing excess tissue pathology.
The enzyme carbonic anhydrase IV is required to regulate the bioenergetic state and antihelminth functions of alveolar macrophages
Category
Poster and Podium (Block Symposium)