Siderocalin inhibits the intracellular replication of Mycobacterium tuberculosis in macrophages |
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| Authors: | Erin E Johnson Chittur V Srikanth reas Sandgren Lynne Harrington Estela Trebicka Lijian Wang Niels Borregaard Megan Murray & Bobby J Cherayil |
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| Institution: | Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA;;Mucosal Immunology Laboratory, Pediatric Gastroenterology Unit, Massachusetts General Hospital, Charlestown, MA, USA;;Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA;;Department of Nutrition, Harvard School of Public Health, Boston, MA, USA;;and Department of Hematology, University of Copenhagen, Copenhagen, Denmark |
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| Abstract: | Siderocalin is a secreted protein that binds to siderophores to prevent bacterial iron acquisition. While it has been shown to inhibit the growth of Mycobacterium tuberculosis ( M.tb ) in extracellular cultures, its effect on this pathogen within macrophages is not clear. Here, we show that siderocalin expression is upregulated following M.tb infection of mouse macrophage cell lines and primary murine alveolar macrophages. Furthermore, siderocalin added exogenously as a recombinant protein or overexpressed in the RAW264.7 macrophage cell line inhibited the intracellular growth of the pathogen. A variant form of siderocalin, which is expressed only in the macrophage cytosol, inhibited intracellular M.tb growth as effectively as the normal, secreted form, an observation that provides mechanistic insight into how siderocalin might influence iron acquisition by the bacteria in the phagosome. Our findings are consistent with an important role for siderocalin in protection against M.tb infection and suggest that exogenously administered siderocalin may have therapeutic applications in tuberculosis. |
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| Keywords: | iron infection lipocalin 2 NGAL |
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