In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 17 ( 2009-04-28), p. 7107-7112
Abstract:
Neutrophils are the most abundant leukocytes in circulation and provide a primary innate immune defense function against bacterial pathogens before development of a specific immune response. These specialized phagocytes are short lived (12–24 hours) and continuously replenished from bone marrow. We found that if the host is overwhelmed by a high inoculum of Listeria monocytogenes, neutrophils are depleted despite high granulocyte-colony stimulating factor induction. In contrast to a low-dose innocuous L. monocytogenes infection, high-dose Listeria challenge blocks neutrophil recruitment to infectious abscesses and bacterial proliferation is not controlled, resulting in lethal outcomes. Administering synthetic TLR2-ligand or heat-killed bacteria during the innocuous L. monocytogenes infection reproduced these effects, once again leading to overwhelming bacterial propagation. The same stimuli also severely aggravated Salmonella typhimurium , Staphylococcus aureus, and Streptococcus pyogenes systemic infection. These data implicate systemic innate immune stimulation as a mechanism of bone marrow neutrophil exhaustion which negatively influences the outcome of bacterial infections.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0901162106
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2009
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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