The control of Leishmania (Leishmania) major by TNF in vivo is dependent on the parasite strain

Abstract

Previous studies provided evidence that the role of TNF in the control of Leishmania (Leishmania) major might vary with the parasite strain. Here, we analyzed the development and outcome of cutaneous leishmaniasis in C57BL/6 wild-type (B6.WT) and TNF-deficient (B6. TNF–/–) mice infected with two different isolates of L. (L.) major (FRIEDLIN vs. BNI). L. (L.) major BNI caused progressive, fatal disease in B6.TNF–/– mice. In contrast, B6.TNF–/– mice infected with the L. (L.) major FRIEDLIN strain exhibited partial resistance characterized by chronic, non-healing skin lesions without lethality. Analysis of the tissue parasite numbers showed that the numbers of L. (L.) major FRIEDLIN and BNI parasites were comparable in footpads and lymph nodes of B6.TNF–/– mice, whereas in the spleen the parasite numbers were strikingly lower in the case of L. (L.) major FRIEDLIN. In vitro, cytokine-activated inflammatory macrophages killed L. (L.) major FRIEDLIN more efficiently than L. (L.) major BNI. These results suggest that in the absence of TNF, the course of leishmaniasis depends on the biology of the inoculated L. (L.) major strain, which most likely explains the previously published discrepant results on the role of TNF in leishmaniasis.