Monocyte and macrophage functions in M-CSF-deficient op/op mice during experimental leishmaniasis.
Mice with a naturally occurring Csfm(op)/Csfm(op) (op/op) gene mutation lack functional macrophage-colony stimulating factor (M-CSF) and are deficient of M-CSF-derived macrophages. They are severely monocytopenic, and their remaining M-CSF-independent macrophages were shown to differ in differentiation and distinct functions when compared with phenotypically normal mice of the same background. It is not known if osteopetrosis mice (op/op mice) are able to mount a specific immune response against intracellular pathogens, as this would require complex effector functions by macrophages. We therefore investigated the ability of op/op mice and their M-CSF-independent macrophages to combat infection with Leishmania major. op/op mice retained the ability to resist an infection with L. major by mounting a T helper cell type 1 cell response, eliminating parasites and resolving the lesions. Macrophages from op/op mice were able to sufficiently perform effector functions in vitro, such as phagocytosis, production of leishmanicidal nitric oxide (NO), killing of parasites, and release of interleukin (IL)-12. There were quantitative differences, as M-CSF-derived macrophages from hematopoietic organs of control mice showed significantly higher rates of phagocytosis and higher NO release after stimulation with lipopolysaccharides than corresponding macrophages from op/op mice. In contrast, when peritoneally elicited macrophages were used, those from op/op mice revealed a stronger response than those from control mice with regard to release of NO or IL-12. These differences suggest that M-CSF-independent maturation of op/op monocytes subsequent to their release from hematopoietic tissue exerts influence on their effector functions. However, M-CSF or M-CSF-derived macrophages are not necessary for an effective immune response against L. major.
Schönlau
Frank
F
Institute of Experimental Dermatology, University of Münster, Germany.
Schlesiger
Christian
C
Ehrchen
Jan
J
Grabbe
Stephan
S
Sorg
Clemens
C
Sunderkötter
Cord
C
Ehrehen
Jan
J
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002478:Cells, Cultured / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006968:Hypersensitivity, Delayed / Q000276:immunology; D018664:Interleukin-12 / Q000378:metabolism; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency* / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D023421:Models, Animal; D009000:Monocytes / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D010022:Osteopetrosis / Q000235:genetics; D010587:Phagocytosis; D012867:Skin / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology
D018664:Interleukin-12; D009569:Nitric Oxide; D016173:Macrophage Colony-Stimulating Factor