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Effect of silica on the susceptibility of mice to experimental histoplasmosis
Abstract:
The role of macrophages in the innate immunity of mice to histoplasmosis was investigated using silica, which selectively inactivates macrophages. Mice given silica IV 1 day prior to challenge with live yeast cells of Histoplasma capsulatum were more susceptible to infection than were untreated controls. This increased susceptibility to Histoplasma was observed when mice were given silica at 1, 14, and 21 days prior to infection but not at 3 and 7 days. Silica treated mice that survived 30 days after challenge with a sublethal dose of Histoplasma had 23 times more viable organisms in their spleens than in those of untreated controls. The blastogenic response of spleen cells to concanavalin A and phytohemagglutinin was unaffected at 12 hr after silica injection but was significantly depressed between 1 and 21 days. In contrast, silica treatment did not affect the blastogenic response of spleen cells to lipopolysaccharide. Silica particles were cytotoxic for mouse peritoneal macrophages but not to lymphocytes in vitro. These results indicate that macrophages play an essential role in natural immunity to histoplasmosis.
Insights
Macrophages are crucial for innate immunity against histoplasmosis. Inactivating macrophages with silica increased susceptibility and fungal burden in mice, highlighting their essential role in host defense.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Macrophages are key immune cells in innate immunity.
- Histoplasmosis is a fungal infection caused by Histoplasma capsulatum.
- Understanding macrophage function is vital for controlling fungal infections.
Purpose of the Study:
- To investigate the role of macrophages in innate immunity against Histoplasma capsulatum infection in mice.
- To determine the effect of macrophage inactivation on susceptibility to histoplasmosis.
Main Methods:
- Mice were treated with silica, a macrophage-inactivating agent, at various time points before infection with Histoplasma capsulatum.
- Susceptibility to infection, fungal burden in spleens, and immune cell responses (blastogenesis) were assessed.
- In vitro experiments evaluated the cytotoxicity of silica particles on macrophages and lymphocytes.
Main Results:
- Silica treatment significantly increased susceptibility to Histoplasma infection and fungal burden in mice.
- Macrophage inactivation by silica impaired the host's ability to control fungal growth.
- Silica treatment depressed spleen cell responses to T-cell mitogens but not B-cell mitogens.
- Silica particles were cytotoxic to macrophages but not lymphocytes in vitro.
Conclusions:
- Macrophages play an essential role in natural immunity to histoplasmosis.
- Inactivation of macrophages compromises the host's defense against Histoplasma capsulatum.
- Targeting macrophages could be a strategy for managing histoplasmosis.