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Modifications of the immune response induced by Histoplasma capsulatum products
B H Ruiz1, R E Carvajal, L Ortiz-Ortiz
1Instituto de Investigaciones Biomédicas, Facultad de Medicina, Universidad Nacional Autónoma de México.
Abstract:
To understand the host-parasite relationship in histoplasmosis, mice were inoculated with histoplasmin (HP), the filtrate of aged cultures of Histoplasma capsulatum, and the immune response of these mice towards sheep red blood cells (SRBC) and to trinitrophenyl hapten was studied. The filtrate abrogated completely the primary antibody response to both antigens as measured by the number of spleen hemolytic plaque forming cells when HP was administered at doses greater than 200 micrograms two days before the antigen. Suppression was elicited by HP when it was injected either intravenously, intraperitoneally, or subcutaneously. Inoculation with HP and antigen on the same day did not result in suppression. The secondary antibody response was not modified at any dose. Variation of the response with time was determined by counting the number of rosette forming cells (RFC) to SRBC every two days for a total of 21 days. Antibody-mediated RFC ('B' rosettes) were depressed throughout the experiment, while the number of non 'B', presumably T, RFC did not vary from control values. In animals inoculated with HP alone, high number of RFC were detected on day 11 after HP inoculation, suggesting that HP may have polyclonal activation effects. These results support the possibility that H. capsulatum evades the immune defenses by induction of a suppressive phenomenon in which the afferent limb of the immune response is not involved. This effect appeared to be induced directly by a product of the fungus, instead of by factors generated during the immune response to this microorganism.
Insights
Histoplasma capsulatum filtrate (HP) suppresses the primary immune response in mice. This immune evasion mechanism appears directly induced by a fungal product, affecting antibody production but not T-cell responses.
Area of Science:
- Immunology
- Mycology
- Host-Parasite Interactions
Background:
- Histoplasmosis is caused by Histoplasma capsulatum, a fungus that can evade host immune defenses.
- Understanding the mechanisms of immune evasion is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the host-parasite relationship in histoplasmosis by examining the effects of Histoplasma capsulatum filtrate (HP) on the murine immune system.
- To determine if HP can suppress immune responses to unrelated antigens and elucidate the nature of this suppression.
Main Methods:
- Mice were inoculated with HP and then challenged with sheep red blood cells (SRBC) and trinitrophenyl hapten.
- Immune responses were measured by quantifying spleen hemolytic plaque-forming cells and rosette-forming cells (RFC).
- Time-course analysis of RFC was performed to differentiate between B-cell and T-cell responses.
Main Results:
- HP administration greater than 200 micrograms, two days before antigen, completely abrogated the primary antibody response to SRBC and trinitrophenyl hapten.
- Suppression occurred regardless of HP administration route (intravenous, intraperitoneal, subcutaneous) but not when given on the same day as the antigen.
- Antibody-mediated RFC were depressed, while T-cell RFC remained unchanged; HP alone induced polyclonal activation of RFC.
Conclusions:
- Histoplasma capsulatum appears to evade immune defenses by inducing a suppressive phenomenon, likely mediated directly by a fungal product.
- This suppression specifically targets the afferent limb of the immune response, affecting B-cell antibody production without impacting T-cell responses.
- The findings suggest a novel immune evasion strategy employed by H. capsulatum.