Mice unresponsive to GM-CSF are unexpectedly resistant to cutaneous Leishmania major infection.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to play a protective role in leishmanial infection. Mice with a null mutation in the gene for the beta common (beta c) chain of the receptors for GM-CSF, interleukin(IL)-3 and IL-5 (beta c-null mice) display normal steady state hemopoiesis and develop lung disease similar to the human condition, alveolar proteinosis, due to a lack of signaling by GM-CSF. We therefore expected to observe a heightened sensitivity to Leishmania major in the beta c-null mice. Surprisingly, the beta c-null mice were more resistant to cutaneous infection than wild-type (wt) mice. Upon intradermal injection of L. major promastigotes, fewer beta c-null mice developed cutaneous lesions than wt mice and these lesions were smaller and healed more rapidly than in wt mice. This resistance to disease was associated with a reduced percentage of in vitro infected beta c-null macrophages. Macrophages from beta c-null mice displayed a more activated phenotype and produced increased amounts of nitric oxide following infection with L. major, both in vivo and in vitro. Paradoxically, however, the parasite burden in the draining lymph nodes was similar in both beta c-null and wt mice, suggesting that at least a subpopulation of cells was susceptible to the parasite. The mechanism preventing normal lesion development remains to be elucidated.
Scott
C L
CL
The Walter and Eliza Hall Institute of Medical Research, Victoria, 3050, Australia.
Roe
L
L
Curtis
J
J
Baldwin
T
T
Robb
L
L
Begley
C G
CG
Handman
E
E
D000818:Animals; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009569:Nitric Oxide / Q000096:biosynthesis; D010533:Peritoneal Lavage; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000235:genetics / Q000378:metabolism; D053649:Receptors, Interleukin-5
D007377:Interleukin-3; D015848:Interleukin-5; D011956:Receptors, Cell Surface; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D053649:Receptors, Interleukin-5; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor