The host resistance locus sst1 controls innate immunity to Listeria monocytogenes infection in immunodeficient mice
Authors
Boyartchuk, Victor L.Rojas, Mauricio
Yan, Bo-Shiun
Jobe, Ousman
Hurt, Nicholas
Dorfman, David M.
Higgins, Darren E.
Dietrich, William F.
Kramnik, Igor
UMass Chan Affiliations
Program in Gene Function and ExpressionDocument Type
Journal ArticlePublication Date
2004-10-08Keywords
AnimalsChromosome Mapping
Genetic Predisposition to Disease
Immunity, Natural
Interferon Type II
Killer Cells, Natural
Listeria Infections
Listeria monocytogenes
Macrophage Activation
Macrophages
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, SCID
Nitric Oxide
Phagocytes
Polymorphism, Genetic
Reactive Oxygen Species
T-Lymphocytes
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Epidemiological, clinical, and experimental approaches have convincingly demonstrated that host resistance to infection with intracellular pathogens is significantly influenced by genetic polymorphisms. Using a mouse model of infection with virulent Mycobacterium tuberculosis (MTB), we have previously identified the sst1 locus as a genetic determinant of host resistance to tuberculosis. In this study we demonstrate that susceptibility to another intracellular pathogen, Listeria monocytogenes, is also influenced by the sst1 locus. The contribution of sst1 to anti-listerial immunity is much greater in immunodeficient scid mice, indicating that this locus controls innate immunity and becomes particularly important when adaptive immunity is significantly depressed. Similar to our previous observations using infection with MTB, the resistant allele of sst1 prevents formation of necrotic infectious lesions in vivo. We have shown that macrophages obtained from sst1-resistant congenic mice possess superior ability to kill L. monocytogenes in vitro. The bactericidal effect of sst1 is dependent on IFN-gamma activation and reactive oxygen radical production by activated macrophages after infection, but is independent of NO production. It is possible that there is a single gene that controls common IFN-dependent macrophage function, which is important in the pathogenesis of infections caused by both MTB and L. monocytogenes. However, host resistance to the two pathogens may be controlled by two different polymorphic genes encoded within the sst1 locus. The polymorphic gene(s) encoded within the sst1 locus that controls macrophage interactions with the two intracellular pathogens remains to be elucidated.Source
J Immunol. 2004 Oct 15;173(8):5112-20.
DOI
10.4049/jimmunol.173.8.5112Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38225PubMed ID
15470055Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.173.8.5112