Open AccessSiderocalin inhibits the intracellular replication of Mycobacterium tuberculosis in macrophages
Author(s) -
Johnson Erin E.,
Srikanth Chittur V.,
Sandgren Andreas,
Harrington Lynne,
Trebicka Estela,
Wang Lijian,
Borregaard Niels,
Murray Megan,
Cherayil Bobby J.
Publication year - 2010
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2009.00622.x
Subject(s) - intracellular , biology , phagosome , macrophage , microbiology and biotechnology , siderophore , intracellular parasite , mycobacterium tuberculosis , extracellular , cell culture , pathogen , cytosol , recombinant dna , bacteria , mycobacterium , tuberculosis , in vitro , biochemistry , gene , enzyme , medicine , genetics , pathology
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.