IMPAIRED RESPONSIVENESS TO GAMMA-INTERFERON OF MACROPHAGES INFECTED WITH LYMPHOCYTIC CHORIOMENINGITIS VIRUS CLONE-13 - SUSCEPTIBILITY TO HISTOPLASMOSIS
L. Villarete et al., IMPAIRED RESPONSIVENESS TO GAMMA-INTERFERON OF MACROPHAGES INFECTED WITH LYMPHOCYTIC CHORIOMENINGITIS VIRUS CLONE-13 - SUSCEPTIBILITY TO HISTOPLASMOSIS, Infection and immunity, 63(4), 1995, pp. 1468-1472
Lymphocytic choriomeningitis virus clone 13 (LCMV clone 13), a variant
isolated from the spleens of neonatally infected mice, causes persist
ent infections in mice infected as adults. Such persistently infected
mice succumb to a normally sublethal dose of Histoplasma capsulatum, a
nd their macrophages contain overwhelming numbers of yeast cells of th
e fungus. Both LCMV clone 13 and H. capsulatum yeast cells target and
replicate in macrophages of the host. We sought to study the effects o
f LCMV clone 13 on the ability of macrophages to control growth of H.
capsulatum in vitro. We show that the growth of H. capsulatum within m
acrophages was not directly affected by the presence of LCMV clone 13,
However, macrophages containing LCMV clone 13 did not respond fully t
o gamma interferon (IFN-gamma) stimulation. Such unresponsiveness resu
lted in proliferation of the fungus within macrophages cultured in the
presence of IFN-gamma. The addition of anti-IFN-alpha/beta antibodies
to LCMV clone 13-infected macrophage cultures restored macrophage res
ponsiveness to IFN-gamma. These results indicate that production of IF
N-alpha/beta by LCMV clone 13-infected macrophages antagonizes their r
esponsiveness to IFN-gamma. Such antagonism may be one of the mechanis
ms by means of which certain viruses cause immune suppression and susc
eptibility to opportunistic infections.