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Chronic infection and reactivation in a pulmonary challenge model of histoplasmosis
M Durkin1, S Kohler, C Schnizlein-Bick
1Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Abstract:
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.
Insights
Histoplasmosis reactivation in mice was triggered by CD4 and CD8 lymphocyte depletion. Even without immune suppression, half of immunocompetent mice developed progressive, fatal histoplasmosis.
Area of Science:
- Immunology
- Infectious Diseases
- Mycology
Background:
- Reactivation of latent infections is a significant concern in immunocompromised individuals, particularly those with Acquired Immunodeficiency Syndrome (AIDS).
- Histoplasmosis, a fungal infection caused by *Histoplasma capsulatum*, can become severe or disseminated in individuals with weakened immune systems.
Purpose of the Study:
- To investigate the role of lymphocyte depletion in reactivating histoplasmosis.
- To determine the long-term course and outcome of histoplasmosis in immunocompetent mice.
Main Methods:
- Depletion of CD4 and/or CD8 lymphocytes in mice following intratracheal *Histoplasma capsulatum* infection.
- Monitoring fungal burden in lungs and spleen after immune suppression.
- Long-term observation of infection progression and mortality in immunocompetent mice.
Main Results:
- CD4 and/or CD8 lymphocyte depletion led to significant reactivation of histoplasmosis, evidenced by increased fungal loads in lungs and spleen.
- In immunocompetent mice, a substantial proportion (16 of 32) developed progressive infection, with some succumbing to the disease over a year after initial infection.
- Healthy-appearing survivors in the immunocompetent group showed sterile cultures, indicating clearance or latency, while ill mice harbored high fungal burdens.
Conclusions:
- Lymphocyte depletion can reactivate latent histoplasmosis.
- A significant percentage of immunocompetent mice experience chronic, progressive, and potentially fatal histoplasmosis, highlighting the challenges in controlling this infection even in the absence of overt immunosuppression.