Immune Response to Aspergillus fumigatus in Compromised Hosts: From Bedside to Bench

Louis YA Chai; Alieke G Vonk; Bart-Jan Kullberg; Mihai G Netea

Disclosures

Future Microbiol. 2011;6(1):73-83. 

In This Article

Abstract and Introduction

Abstract

The relevance of studies aimed at understanding host immune response against Aspergillus fumigatus takes on much significance given that all patients with invasive aspergillosis are invariably immunocompromised. This article attempts to correlate relevant findings from recent experimental studies to clinical observations made by the physician at the bedside. It is hoped that the increased understanding of host–fungus immune interaction may pave the way for the development of new management strategies against this difficult-to-treat fungal disease.

Introduction

Invasive aspergillosis (IA) is the most common opportunistic mold infection in patients undergoing hematopoietic stem cell transplantation (HSCT) or chemotherapy for malignancy.[1,2] The incidence of IA is estimated to be between 5 and 10% in recipients of allogenic-HSCT and in patients undergoing chemotherapy for acute leukemia.[1,3,4] In patients receiving intensive chemotherapy for acute myeloid leukemia (AML), the risk of developing IA may be higher.[5] Fundamentally, this is due to the inability of the susceptible host to mount an effective defense against the pathogen following profound immune suppression from underlying disease or iatrogenically from treatment. Despite advances in transplantation protocols, the availability of new antifungal agents and improved strategies of antifungal prophylaxis, morbidity and mortality from IA remain high.[6]

The aim of studying host immune response to Aspergillus, both in the in vitro and in vivo settings, is to identify immune defects inherent in the susceptible host and to elucidate escape mechanisms adopted by the pathogen to evade host immune detection. Recent studies have led to an increased understanding of the immune pathogenesis of infection with Aspergillus fumigatus, the fungal pathogen primarily responsible for IA, although many questions still remain unanswered. However, translating the findings from basic bench research to clinical applications for improved diagnosis and treatment at the bedside may be challenging. This article presents a synthesis of the results from recent bench studies based on current clinical knowledge of IA from the perspective of the physician at the bedside. We will attempt to decipher the implications of these findings so as to harness this knowledge in the development of new management strategies for IA and pave the way for the use of immunotherapy in the foreseeable future.

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