Hemophagocytic Macrophages in Murine Typhoid Fever Have an Anti-Inflammatory Phenotype

Autor: Melissa W. McCoy, Corrella S. Detweiler, Sarah M. Moreland
Rok vydání: 2012
Předmět:
Zdroj: Infection and Immunity. 80:3642-3649
ISSN: 1098-5522
0019-9567
Popis: Histiocytes are white blood cells of the monocytic lineage and include macrophages and dendritic cells. In patients with a variety of infectious and noninfectious inflammatory disorders, histiocytes can engulf nonapoptotic leukocytes and nonsenescent erythrocytes and thus become hemophagocytes. We report here the identification and characterization of splenic hemophagocytes in a natural model of murine typhoid fever. The development of a flow-cytometric method allowed us to identify hemophagocytes based on their greater than 6N (termed 6N+) DNA content. Characterization of the 6N+ population from infected mice showed that these cells consist primarily of macrophages rather than dendritic cells and contain T lymphocytes, consistent with hemophagocytosis. Most 6N+ macrophages from Salmonella enterica serovar Typhimurium-infected mice contain intact DNA, consistent with hemophagocytosis. In contrast, most 6N+ macrophages from control mice or mice infected with a different bacterial pathogen, Yersinia pseudotuberculosis , contain damaged DNA. Finally, 6N+ splenic macrophages from S . Typhimurium-infected mice express markers consistent with an anti-inflammatory M2 activation state rather than a classical M1 activation state. We conclude that macrophages are the predominant splenic hemophagocyte in this disease model but not in Y. pseudotuberculosis -infected mice. The anti-inflammatory phenotype of hemophagocytic macrophages suggests that these cells contribute to the shift from acute to chronic infection.
Databáze: OpenAIRE