Chronic infection and reactivation in a pulmonary challenge model of histoplasmosis.
Reactivation may be a mechanism for the development of histoplasmosis in AIDS. In this study, histoplasmosis was reactivated by the depletion of CD4 and CD8 lymphocytes in mice. CD4 and/or CD8 depletion beginning 1 month after intratracheal infection and continuing for 2 months caused reactivation with a 2.1 log/g increase in the lungs and a 1.5 log increase in the spleen of B6C3F1 mice. Because control animals showed persistent infection, a subsequent experiment sought to determine the long-term outcome in competent mice. Twelve of 32 immunocompetent mice died at weeks 26-52 of infection, and 4 survivors appeared to be clinically ill; all ill mice had high fungus burdens, whereas cultures were sterile in the healthy mice. Eight of the surviving healthy-appearing mice underwent autopsy 2 years after infection, and cultures were sterile. Thus, 16 of 32 immunocompetent mice exhibited progressive infection. CD4 and/or CD8 depletion exacerbated infection, but a chronic progressive and ultimately fatal infection occurred in half the immunocompetent mice.
Durkin
M
M
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Kohler
S
S
Schnizlein-Bick
C
C
LeMonte
A
A
Connolly
P
P
Goldberg
J
J
Garringer
T
T
Wheat
L J
LJ
D000704:Analysis of Variance; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology; D006660:Histoplasmosis / Q000276:immunology*; D007121:Immunocompetence; D016867:Immunocompromised Host / Q000276:immunology*; D051379:Mice; D011897:Random Allocation; D012008:Recurrence; D017741:Survivors