Impaired macrophage leishmanicidal activity at cutaneous temperature.
Temperature is one of the primary influences upon the pathogenesis of cutaneous leishmaniasis. In this study, we measured the temperature of murine leishmanial lesions and determined the ability of lymphokine (LK) activated macrophages to kill Leishmania major at these temperatures. The temperature of leishmanial lesions in BALB/c and C3H/HeN mice ranged from 27 degrees C to 32 degrees C. We found that LK activated resident or inflammatory macrophages exhibited significantly less leishmanicidal activity in vitro at temperatures closer to those measured in vivo. The decrease in microbicidal activity was not due to the enhanced growth of the parasites at lower temperatures, since impaired killing was also observed against non-replicating radiation attenuated amastigotes. Finally, the tumoricidal activity of macrophages was found to be significantly depressed at temperatures below 37 degrees C, indicating a generalized impairment of macrophage function at these temperatures. These findings suggest that impaired macrophage microbicidal activity at cutaneous temperatures may contribute to parasite survival, and imply that healing of leishmanial lesions, as well as other cutaneous infections, may require an exceptionally potent local LK response.
D000818:Animals; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D007896:Leishmaniasis / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology; D012867:Skin / Q000503:physiopathology; D013696:Temperature