Innate immune-induced depletion of bone marrow neutrophils aggravates systemic bacterial infections

Navarini, Alexander A. and Lang, Karl S. and Verschoor, Admar and Recher, Mike and Zinkernagel, Annelies S. and Nizet, Victor and Odermatt, Bernhard and Hengartner, Hans and Zinkernagel, Rolf M.. (2009) Innate immune-induced depletion of bone marrow neutrophils aggravates systemic bacterial infections. Proceedings of the National Academy of Sciences of the United States of America, 106 (17). pp. 7107-7112.

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Spezialf├Ącher (Klinik) > Dermatologie USB > Dermatologie (Navarini)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialf├Ącher (Klinik) > Dermatologie USB > Dermatologie (Navarini)
UniBasel Contributors:Navarini, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Sep 2020 09:44
Deposited On:30 Sep 2020 09:44

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