Immunotherapy of Cryptococcus infections

C. Antachopoulos, T. J. Walsh

Research output: Contribution to journalReview articlepeer-review

Abstract

Despite appropriate antifungal treatment, the management of cryptococcal disease remains challenging, especially in immunocompromised patients, such as human immunodeficiency virus-infected individuals and solid organ transplant recipients. During the past two decades, our knowledge of host immune responses against Cryptococcus spp. has been greatly advanced, and the role of immunomodulation in augmenting the response to infection has been investigated. In particular, the role of 'protective' Th1 (tumour necrosis factor-α, interferon (IFN)-γ, interleukin (IL)-12, and IL-18) and Th17 (IL-23 and IL-17) and 'non-protective' Th2 (IL-4, IL-10, and IL-13) cytokines has been extensively studied invitro and in animal models of cryptococcal infection. Immunomodulation with monoclonal antibodies against the capsular polysaccharide glucuronoxylomannan, glucosylceramides, melanin and β-glucan and, lately, with radioimmunotherapy has also yielded promising results in animal models. As a balance between sufficiently protective Th1 responses and excessive inflammation is important for optimal outcome, the effect of immunotherapy may range from beneficial to deleterious, depending on factors related to the host, the infecting organism, and the immunomodulatory regimen. Clinical evidence supporting immunomodulation in patients with cryptococcal infection remains too limited to allow firm recommendations. Limited human data suggest a role for IFN-γ. Identification of surrogate markers characterizing patients' immunological status could possibly suggest candidate patients for immunotherapy and the type of immunomodulation to be administered.

Original languageEnglish (US)
Pages (from-to)126-133
Number of pages8
JournalClinical Microbiology and Infection
Volume18
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Cryptococcus
  • Cytokines
  • HIV
  • Immunotherapy
  • Interferon-γ
  • Monoclonal antibodies

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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