Immune responses to invasive aspergillosis: new understanding and therapeutic opportunities

Abstract

Purpose of review Invasive aspergillosis is a worldwide disease that primarily affects immune-compromised patients, agricultural workers with corneal abrasions, individuals with structural lung disease, and patients with primary immune deficiency. The critical function of the immune system is to prevent the germination of airborne conidia into tissue-invasive hyphae. This review covers recent advances that shape our understanding of anti-Aspergillus immunity at the molecular and cellular level. Recent findings Host defense against conidia and hyphae occurs via distinct molecular mechanisms that involve intracellular and extracellular killing pathways, as well as cooperation between different myeloid cell subsets. The strength and efficacy of the host response is shaped by the tissue microenvironment. In preclinical models of disease, host immune augmentation strategies have yielded benefits, yet translating these insights into therapeutic strategies in humans remains challenging. Summary Although advances in early diagnostic strategies and in antifungal drugs have ameliorated clinical outcomes of invasive aspergillosis, further improvements depend on gaining deeper insight into and translating advances in anti-Aspergillus immunity.

Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients

“…The initiation of an efficient antifungal immune response depends on a complex set of signals circulating within the microenvironment, including cytokines and chemokines (Hohl, 2017 ). Understanding how each of these pathways is regulated is essential to uncover the molecular and cellular processes underlying the pathogenesis of IPA, and may also offer crucial insights toward the identification of molecules that correlate strongly with infection and the network of signals that could be therapeutically targeted.…”

Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells

“…Improvements in vector design have recently increased the efficiency of this approach, and the avidity of the TCR has been improved by substituting amino acids in its complementarity determining region and introducing cysteines to form disulfide bonds, thereby preventing α- and β-chain mispairing. TCR-mediated T-cell responses to fungal antigens have been documented in both in vitro and in vivo studies ( 130 , 131 ).…”

The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence

“…Resident alveolar macrophages of the innate immune system are the first line of defence against invading A . fumigatus conidia[ 2 ]. Upon phagocytosis of conidia, macrophages release an array of chemokines and cytokines, resulting in the recruitment of additional white blood cells, such as neutrophil granulocytes[ 2 , 3 ].…”