Foci of Listeria monocytogenes persist in the bone marrow

Abstract

SUMMARYMurine listeriosis is one of the most comprehensive and well-studied models of infection, and Listeria monocytogenes has provided seminal information regarding bacterial pathogenesis. However, many aspects of the mouse model remain poorly understood, including carrier states and chronic colonization which represent important features of the spectrum of host-pathogen interaction. Bone marrow has recently been shown to harbor L. monocytogenes, which spreads from this location to the central nervous system. Bone could, therefore, be an important chronic reservoir, but this infection is difficult to study because it involves only a few bacteria and the extent of infection cannot be assessed until after the animal is sacrificed. We employed in vivo bioluminescence imaging to localize L. monocytogenes bone infections over time in live mice, revealing that the bacteria grow in discrete foci. These lesions can persist in many locations in the legs of mice and are not accompanied by a histological indication such as granuloma or a neutrophil infiltratate. We demonstrate that highly attenuated hly mutants, which have defective intracellular replication, are capable of prolonged focal infection of the bone marrow for periods of up to several weeks. These results support the recently proposed hypothesis that the bone marrow is a unique niche for L. monocytogenes.

Survival of Bactericidal Antibiotic Treatment by a Persister Subpopulation of Listeria monocytogenes

“…During infection, clinical symptoms of listeriosis often appear after a long incubation time (26,27), and the bacterium survives the host immune system for extended periods. Using a bio-luciferase-tagged L. monocytogenes, Hardy et al (58,59) found the bacteria were undetectable in mice for up to 15 days prior spreading to gallbladder, bone marrow, etc., and they suggested that the persisting bacteria were dormant during this period (59). L. monocytogenes enters the host by crossing the gastrointestinal barrier, and it quickly translocate to the spleen and liver, where it grows intracellularly in macrophages (25).…”

Augmented Macrophage Differentiation and Polarization of Tumor-associated Macrophages Towards M1 Subtype in Listeria-administered Tumor-bearing Host

“…9,37,38 Considering the previous reports where augmented tumor infiltration of macrophages has been correlated to an elevated myelopoietic differentiation of BMC, 10,39 we next checked if Listeria infection could alter the process of differentiation of macrophages from precursor BMC in a tumor-bearing host. Indeed, the results of the present study demonstrate an augmented bone marrow cellularity, improved BMC survival accompanied by an inhibition of proapoptotic PUMA expression, and enhanced macrophage colony-forming ability.…”

“…7,8 Thus, one of the targets of tumor immunotherapy is to usher repolarization of TAM to M1 subtype. 7,8 Reports also indicate that after Listerial infection, the bacterial load is significantly high in vital organ systems including bone marrow, 9 which is involved in differentiation of macrophages. Nevertheless, evidences suggest that bone marrow myelopoiesis is one of the important sources of TAM.…”

Osteoarticular tissue infection and development of skeletal pathology in murine brucellosis

“…BLI allows spatiotemporal identification of infectious foci in living hosts (Contag et al, 1995; Doyle et al, 2004). This technique allows us to decisively indicate the presence of metabolically active bacteria in deep tissues of mice (Hardy et al, 2009). …”