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, alveo lar proteinosis, due to a lack of signaling by GM-CSE 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 m ice 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 d isplayed a more activated phenotype and produced increased amounts of nitri c oxide following infection with L. major, both in vivo and in vitro. Parad oxically, however, the parasite burden in the draining lymph nodes was simi lar in both beta c-null and wt mice, suggesting that at least a subpopulati on of cells was susceptible to the parasite. The mechanism preventing norma l lesion development remains to be elucidated. (C) 2000 Editions scientifiq ues et medicales Elsevier SAS.