Cryptococcus neoformans Infection in the Central Nervous System: The Battle between Host and Pathogen

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus with a global distribution. Humans become infected by inhaling the fungus from the environment, and the fungus initially colonizes the lungs. If the immune system fails to contain C. neoformans in the lungs, the fungus can disseminate to the blood and invade the central nervous system, resulting in fatal meningoencephalitis particularly in immunocompromised individuals including HIV/AIDS patients. Following brain invasion, C. neoformans will encounter host defenses involving resident as well as recruited immune cells in the brain. To overcome host defenses, C. neoformans possesses multiple virulence factors capable of modulating immune responses. The outcome of the interactions between the host and C. neoformans will determine the disease progression. In this review, we describe the current understanding of how C. neoformans migrates to the brain across the blood–brain barrier, and how the host immune system responds to the invading organism in the brain. We will also discuss the virulence factors that C. neoformans uses to modulate host immune responses.https://doi.org/10.3390/jof810106

Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Clinical Studies to Animal Experiments

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.https://doi.org/10.3390/microorganisms1012241

Neuroimaging features of primary central nervous system post-transplantation lymphoproliferative disorder following hematopoietic stem cell transplant in patients with β-thalassemia: a case series and review of literature

Abstract Purpose Primary central nervous system post-transplantation lymphoproliferative disorder (PCNS-PTLD) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT) in patients with severe β-thalassemia. This study aimed to assess the clinical presentation, pathological characteristics, neuroimaging findings, and treatment strategies in patients with β-thalassemia who developed PCNS-PTLD and to compare a case series from our transplant center to reported cases from literature. Methods We retrospectively reviewed our hospital database and identified four cases of pathologically confirmed PCNS-PTLD without a history of systemic PTLD in patients with severe β-thalassemia after HSCT. We also performed a relevant literature review on PCNS-PTLD. Results The median time from transplantation to diagnosis of PCNS-PTLD was 5.5 months. Intracerebral lesions were usually multiple involving both supratentorial and infratentorial regions with homogeneous or rim enhancement. All patients had pathologically confirmed PCNS-PTLD with three patients having diffuse large B-cell lymphoma and the fourth patient having plasmacytic hyperplasia. There was low response to treatment with a median survival of 83 days. Conclusion PCNS-PTLD should be considered in the differential diagnosis of patients with β-thalassemia who had an intracranial lesion on neuroimaging after HSCT. Critical relevance statement This case series with a comprehensive review of neuroimaging and clinical characteristics of children with primary central nervous system post-transplantation lymphoproliferative disorder should advance our understanding and improve management of this rare yet severe complication following transplant for β-thalassemia. Key points • We assessed clinical presentation, treatment strategies, and neuroimaging characteristics of PCNS-PTLD in patients with β-thalassemia after transplantation. • Patients with β-thalassemia may have post-transplantation lymphoproliferative disorder presenting as brain lesions on neuroimaging. • Neuroimaging findings of the brain lesions are helpful for prompt diagnosis and proper management. Graphical Abstrac