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Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
09:57

Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens

Published on: February 15, 2011

Apoptosis modulates protective immunity to the pathogenic fungus Histoplasma capsulatum

Holly L Allen1, George S Deepe

  • 1Division of Infectious Diseases, Veterans Affairs Hospital, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

The Journal of Clinical Investigation
|September 10, 2005
PubMed

Insights

Apoptosis, programmed cell death, is crucial for fighting Histoplasma capsulatum fungal infections. Inhibiting apoptosis increases susceptibility to infection, while promoting it reduces fungal burden.

Area of Science:

  • Immunology
  • Mycology
  • Cell Biology

Background:

  • Pathogen-induced apoptosis of lymphocytes correlates with increased infection susceptibility.
  • Host resistance mechanisms against fungal pathogens are not fully understood.

Purpose of the Study:

  • To investigate the role of apoptosis in host resistance against Histoplasma capsulatum infection.
  • To determine the impact of modulating apoptosis on fungal burden and immune responses.

Main Methods:

  • Monitoring leukocyte apoptosis in the lungs of mice infected with H. capsulatum.
  • Utilizing genetically modified mice (gld/gld, TNF-alpha-deficient) and pharmacological inhibitors (caspase inhibitors, suramin).
  • Quantifying fungal burden and measuring cytokine levels (IL-4, IL-10).

Main Results:

  • Leukocyte apoptosis, particularly T cells, increased during H. capsulatum infection.
  • Inhibition of apoptosis (in gld/gld, TNF-alpha-deficient mice, or with caspase inhibitors) led to increased fungal burden.
  • Administration of a pro-apoptotic agent (suramin) reduced fungal burden.
  • Caspase inhibition elevated IL-4 and IL-10 levels, exacerbating infection severity, an effect abrogated in the absence of these cytokines.

Conclusions:

  • Apoptosis is a critical component of protective immunity against Histoplasma capsulatum.
  • Elevated IL-4 and IL-10 levels, associated with inhibited apoptosis, worsen H. capsulatum infection.
  • Targeting apoptosis pathways may offer therapeutic strategies for fungal infections.

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