Affiliation:
1. Departments of Developmental and Molecular Biology and Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, New York, New York 10461
Abstract
ABSTRACT
Listeria monocytogenes
, a facultative intracellular bacterium, has been used extensively to study innate immune responses. Macrophages act as hosts for this bacterium as well as a major defense against it. Using mice homozygous for a null mutation (
Csf1
op
) in the gene for the mononuclear phagocytic growth factor colony-stimulating factor 1 (CSF-1), we have demonstrated that CSF-1-regulated macrophages were essential to defend against a listerial infection. In the absence of CSF-1, monocytes were not recruited to the sites of infection due to the lack of synthesis of the macrophage chemoattractant chemokine MCP-1. In addition, there was no burst of interleukin-10 (IL-10) synthesis that has been shown to result in the egress of neutrophils from sites of infection. Consequently, neutrophils were not replaced by macrophages, and numerous neutrophil-filled microabscesses developed, followed by tissue destruction and death of the mice. In the CSF-1 nullizygous mice compared to wild-type mice, there was also a very low synthesis of gamma interferon (IFN-γ), resulting in reduced macrophage activation. However, the concentrations of the IFN-γ-inducing cytokines IL-12 and IL-18 at this bacterial load were similar in these mutant mice. In contrast, IL-6 concentrations were dramatically reduced. Administration of IL-6 to
Csf1
op
/Csf1
op
mice significantly increased the synthesis of IFN-γ and reduced the bacterial burden to a greater extent than treatment with IFN-γ alone. These data indicate that IL-6 occupies a central role in the CSF-1-regulated macrophage response to
L. monocytogenes
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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