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Published on: June 22, 2019
Cannabinoid-mediated exacerbation of brain infection by opportunistic amebae
Guy A Cabral1, Francine Marciano-Cabral
1Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298-0678, USA. gacabral@hsc.vcu.edu
Abstract:
Recent reports indicate a higher frequency of brain infections with opportunistic amebae of the genus Acanthamoeba among immune compromised individuals, including AIDS patients. We have demonstrated, using a murine model of Granulomatous Amebic Encephalitis (GAE), that the major psychoactive and immune suppressive component in marijuana delta-9-tetrahydrocannabinol (THC) exacerbates infection by these amebae. Mice administered THC and infected with Acanthamoeba exhibited dose-related higher mortalities than infected vehicle controls. The greater severity of disease for THC-treated mice was accompanied by decreased accumulation of macrophage-like cells at focal sites of infection in the brain. Furthermore, THC administration resulted in decreased levels of mRNA for the pro-inflammatory cytokines interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor alpha for neonatal rat microglia co-cultured with Acanthamoeba. These results indicate a potential for marijuana to alter the capacity of brain macrophage-like cells to mount a full complement of immune responsiveness to brain infection by opportunistic amebae.
Insights
Delta-9-tetrahydrocannabinol (THC), a component of marijuana, worsens brain infections caused by Acanthamoeba in mice. This immune suppression by THC may reduce the brain
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Opportunistic amebic brain infections, like Granulomatous Amebic Encephalitis (GAE), pose a significant threat to immunocompromised individuals.
- The genus Acanthamoeba includes opportunistic amebae capable of causing severe central nervous system infections.
Purpose of the Study:
- To investigate the effect of delta-9-tetrahydrocannabinol (THC), a major psychoactive component of marijuana, on Acanthamoeba infections in the brain.
- To determine if THC exacerbates Granulomatous Amebic Encephalitis (GAE) and impacts the brain's immune response.
Main Methods:
- A murine model of Granulomatous Amebic Encephalitis (GAE) was utilized.
- Mice were administered varying doses of delta-9-tetrahydrocannabinol (THC) before and during infection with Acanthamoeba.
- Histological analysis assessed the accumulation of macrophage-like cells at infection sites.
- Real-time quantitative PCR measured mRNA levels of pro-inflammatory cytokines (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor alpha) in microglia co-cultured with Acanthamoeba.
Main Results:
- THC administration led to a dose-related increase in mortality in infected mice compared to controls.
- THC-treated mice showed reduced accumulation of macrophage-like cells in brain lesions.
- In vitro, THC exposure decreased pro-inflammatory cytokine mRNA levels in microglia exposed to Acanthamoeba.
Conclusions:
- Delta-9-tetrahydrocannabinol (THC) exacerbates Acanthamoeba-induced brain infections, potentially by suppressing the immune response.
- THC may impair the ability of brain macrophage-like cells to effectively combat opportunistic amebic infections.
- These findings highlight a potential risk associated with marijuana use in immunocompromised individuals susceptible to amebic encephalitis.
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