title: Hemophagocytic macrophages in murine typhoid fever have an anti-inflammatory phenotype.
abstract: 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.
authors.affiliation: Department of Molecular Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA.
authors.forename: Melissa W
authors.initials: MW
authors.lastname: McCoy
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Moreland
authors.forename: Corrella S
authors.initials: CS
authors.lastname: Detweiler
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology*; D008264:Macrophages / Q000145:classification / Q000502:physiology*; D051379:Mice; D010587:Phagocytosis / Q000502:physiology*; D012486:Salmonella typhimurium / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014435:Typhoid Fever / Q000276:immunology / Q000473:pathology*; D015011:Yersinia pseudotuberculosis / Q000276:immunology; D015012:Yersinia pseudotuberculosis Infections / Q000276:immunology