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Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Clinical Studies to Animal Experiments
Zoe W Shi1,2, Yanli Chen1, Krystal M Ogoke1
1Division of Immunology, Virginia-Maryland College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742, USA.
Abstract:
Cryptococcus neoformans is an encapsulated pathogenic fungus that initially infects the lung but can migrate to the central nervous system (CNS), resulting in meningoencephalitis. The organism causes the CNS infection primarily in immunocompromised individuals including HIV/AIDS patients, but also, rarely, in immunocompetent individuals. In HIV/AIDS patients, limited inflammation in the CNS, due to impaired cellular immunity, cannot efficiently clear a C. neoformans infection. Antiretroviral therapy (ART) can rapidly restore cellular immunity in HIV/AIDS patients. Paradoxically, ART induces an exaggerated inflammatory response, termed immune reconstitution inflammatory syndrome (IRIS), in some HIV/AIDS patients co-infected with C. neoformans. A similar excessive inflammation, referred to as post-infectious inflammatory response syndrome (PIIRS), is also frequently seen in previously healthy individuals suffering from cryptococcal meningoencephalitis. Cryptococcal IRIS and PIIRS are life-threatening complications that kill up to one-third of affected people. In this review, we summarize the inflammatory responses in the CNS during HIV-associated cryptococcal meningoencephalitis. We overview the current understanding of cryptococcal IRIS developed in HIV/AIDS patients and cryptococcal PIIRS occurring in HIV-uninfected individuals. We also describe currently available animal models that closely mimic aspects of cryptococcal IRIS observed in HIV/AIDS patients.
Insights
Cryptococcus neoformans causes meningoencephalitis, particularly in HIV/AIDS patients. Antiretroviral therapy can trigger dangerous immune responses like IRIS and PIIRS, highlighting the need for better management strategies.
Area of Science:
- Mycology
- Immunology
- Neuroscience
Background:
- Cryptococcus neoformans is a fungal pathogen that can cause meningoencephalitis, especially in immunocompromised individuals like HIV/AIDS patients.
- Impaired cellular immunity in HIV/AIDS patients limits fungal clearance, while antiretroviral therapy (ART) can paradoxically trigger exaggerated inflammatory responses.
- Immune reconstitution inflammatory syndrome (IRIS) in HIV/AIDS patients and post-infectious inflammatory response syndrome (PIIRS) in HIV-uninfected individuals are life-threatening complications of cryptococcal meningoencephalitis.
Purpose of the Study:
- To review inflammatory responses in the central nervous system (CNS) during HIV-associated cryptococcal meningoencephalitis.
- To provide an overview of the current understanding of cryptococcal IRIS in HIV/AIDS patients and cryptococcal PIIRS in HIV-uninfected individuals.
- To describe animal models that mimic cryptococcal IRIS in HIV/AIDS patients.
Main Methods:
- Literature review of inflammatory responses in CNS cryptococcal meningoencephalitis.
- Synthesis of current knowledge on cryptococcal IRIS and PIIRS.
- Evaluation of existing animal models for cryptococcal IRIS.
Main Results:
- Cryptococcal meningoencephalitis involves complex inflammatory responses in the CNS.
- IRIS and PIIRS represent severe, potentially fatal inflammatory complications.
- Animal models offer insights into cryptococcal IRIS mechanisms.
Conclusions:
- Understanding CNS inflammation is crucial for managing cryptococcal meningoencephalitis.
- IRIS and PIIRS pose significant risks and require further investigation and therapeutic strategies.
- Animal models are valuable tools for studying cryptococcal IRIS and developing interventions.
