N. Kudeken et al., DIFFERENT SUSCEPTIBILITIES OF YEASTS AND CONIDIA OF PENICILLIUM-MARNEFFEI TO NITRIC-OXIDE (NO)-MEDIATED FUNGICIDAL ACTIVITY OF MURINE MACROPHAGES, Clinical and experimental immunology, 112(2), 1998, pp. 287-293
Penicillium marneffei is an important opportunistic fungal pathogen. H
ost defence mechanisms against P. marneffei are not fully understood.
We investigated the fungicidal activity of murine peritoneal macrophag
es against two forms of P. marneffei, conidia and yeast cells, and the
involvement of the NO-mediated killing system. Peritoneal macrophages
suppressed the intracellular, growth of P. marneffei yeast cells and
conidia. The number of live yeast cells within macrophages was signifi
cantly reduced by activation of macrophages by interferon-gamma (IFN-g
amma), while a similar response was not observed with conidia. IFN-gam
ma-induced macrophage fungicidal activity against yeast cells was medi
ated by NO and was almost completely inhibited by N-G-monomethyl-L-arg
inine (L-NMMA), a competitive inhibitor of NO synthesis, while N-G-mon
omethyl-D-arginine (D-NMMA), an optical isomer of L-NMMA, did not show
any influence. NO production by macrophages stimulated with IFN-gamma
was significantly enhanced when these macrophages were cultured with
P. marneffei yeast cells, while conidia did not enhance macrophage NO
production. Furthermore, yeast cells were more susceptible to the kill
ing effect of chemically generated NO than conidia. Our results indica
te that the yeast form of P. marneffei is more sensitive to the fungic
idal activity of IFN-gamma-stimulated macrophages than conidia, and su
ggest that the different effects of two forms of P, marneffei on macro
phage NO production and their different susceptibilities to NO may be
reasons for the present findings.