Current Fungal Infection Reports

, 5:252

Cryptococcus-Related Immune Reconstitution Inflammatory Syndrome (IRIS): Pathogenesis and its Clinical Implications

Genomics and Pathogenesis (Shmuel Shoham, Section Editor)

DOI: 10.1007/s12281-011-0064-8

Cite this article as:
Wiesner, D.L. & Boulware, D.R. Curr Fungal Infect Rep (2011) 5: 252. doi:10.1007/s12281-011-0064-8


This review provides an overview of Cryptococcus neoformans immunology and focuses on the pathogenesis of Cryptococcus-related paradoxical immune reconstitution inflammatory syndrome (IRIS). Cryptococcal IRIS has three phases: (1) before antiretroviral therapy (ART), with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance; (2) during initial ART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and (3) at IRIS, a cytokine storm with a predominant type-1 helper T-cell (Th1) interferon-gamma (IFN-γ) response. Understanding IRIS pathogenesis allows for risk stratification and customization of HIV/AIDS care. In brief, persons at high IRIS risk may benefit from enhancing microbiologic clearance by use of adjunctive agents in combination with amphotericin, prolonging initial induction therapy, and/or increasing the initial consolidation antifungal therapy dose to at least 800 mg of fluconazole daily until the 2-week CSF culture is known to be sterile. Prophylactic anti-inflammatory therapies or undue delay of ART initiation in an attempt to prevent IRIS is unwarranted and may be dangerous.


HIVAIDSCryptococcal meningitisCM-IRISImmune reconstitution inflammatory syndromePathogenesisReviewAntiretroviral therapyImmunologyRisk stratificationBiomarkersAntifungal therapyAnti-inflammatory therapy

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Division of Infectious Disease & International Medicine, Department of MedicineUniversity of MinnesotaMinneapolisUSA