Functional Competence of Peritoneal Macrophages in Murine Lyme Borreliosis

Abstract

In mice infected with the Lyme disease spirochete, Borrelia burgdorferi, spirochetes can be cultured from the uninflamed peritoneal cavity despite their proximity to resident macrophages. Here we have evaluated the phagocytic and killing capacity of peritoneal macrophages ex vivo from such mice, and compared them to cells from uninfected controls. We noted no significant differences in the numbers of cells recovered from lavage fluid nor in the proportion of lymphocytes in that fluid or their type or state of activation; B cells vs. T cells, CD4 vs. CD8, T cell receptor display (TCRαβ vs. TCRγδ), or B cell activation markers (CD24 vs. CD44). In addition, in studies conducted with coded samples, macrophages from infected animals were similar to controls in their ability (i) to bind and ingest spirochetes as shown by immunofluorescent kinetic studies imaged by confocal microscopy, (ii) to kill spirochetes as detected by acridine orange vital staining in live confocal microscopy, and (iii) to generate H₂O₂, a measure of their activation. Finally, we observed no difference in the ability of cells isolated from infected mice to kill the parasite, Toxoplasma gondii, a sensitive functional measure of the activation of killing capacity. Thus, despite the failure of immune clearance that results in persistent or chronic disease in vivo, there does not appear to be a global impairment of macrophage function in the infected host. It remains to be determined whether specific sites of inflammation, e.g., skin, joints, heart, are associated with a downregulation of phagocyte function locally.