Related Experiment Video
Updated: Aug 8, 2026
Murine Model of CD40-activation of B cells
Published on: March 6, 2010
Effect of CD40 ligand on the course of murine histoplasmosis
L J Wheat1, M Durkin, C Schnizlein-Bick
1Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. jwheat@miravista.com
Insights
CD40 ligand (CD40L) showed minimal impact on recovery from histoplasmosis in mice. This study found CD40L did not improve fungal clearance or synergize with amphotericin B treatment.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- CD40 ligand (CD40L)-CD40 interaction is crucial for T-cell mediated immunity.
- Histoplasmosis is a fungal infection that can cause severe illness.
Purpose of the Study:
- To investigate the role of CD40L in host recovery from histoplasmosis.
- To evaluate CD40L's efficacy alone and in combination with amphotericin B in a murine model.
Main Methods:
- Mice were infected intratracheally with Histoplasma capsulatum.
- Treatment with CD40L and/or amphotericin B was administered at various time points.
- Fungal burden in lungs and spleen, and cytokine levels (IFN-gamma, IL-12, IL-10) were assessed.
Main Results:
- CD40L treatment alone resulted in less than a one-log reduction in fungal burden when initiated pre-infection.
- CD40L did not show synergistic effects with low-dose amphotericin B in CD4-depleted mice.
- Neither CD40L nor amphotericin B, alone or combined, effectively lowered fungal burden in a more virulent infection model.
Conclusions:
- CD40L demonstrated minimal to no beneficial effect on the course of histoplasmosis in this murine model.
- The findings suggest CD40L is not a viable therapeutic strategy for histoplasmosis, even with antifungal treatment.
Abstract:
CD40 ligand-CD40 ligation is important in the development of T-cell-mediated immune responses. The purpose of this study was to examine the role of CD40L in recovery from histoplasmosis using a murine model of intratracheally induced infection. B6C3F1 mice were infected intratracheally with Histoplasma capsulatum yeast and monitored for clearance of the organism from the lungs and spleen. CD40L treatment was begun on either day -2 or +2 post inoculation and continued until day 14 in CD4-depleted animals and from day -2 to day +4 in non-immunosuppressed animals. Amphotericin B treatment was begun four days following inoculation and given every other day for 10 days. CD40L reduced fungal burden by less than one log when started two days before infection but did not act synergistically with low-dosage amphotericin B (0.2 mg kg(-1) qod) in CD4 depleted mice. Low-dose amphotericin B, CD40L, and the combination of the two failed to lower the fungal burden in a second experiment using a more virulent isolate of the same strain of H. capsulatum in CD4-depleted mice. Furthermore, CD40L did not increase the concentrations of IFN-gamma, IL-12 or IL-10 in the lungs or spleens of infected animals. In summary, CD40L had minimal or no effect on the course of infection in this murine model of histoplasmosis.
