New advances in invasive aspergillosis immunobiology leading the way towards personalized therapeutic approaches

Abstract

Invasive aspergillosis (IA) remains a devastating disease in immune compromised patients despite significant advances in our understanding of fungal virulence and host defense mechanisms. In this review, we summarize important research advances in the fight against IA with particular focus on early events in the interactions between Aspergillus fumigatus and the host that occur in the respiratory tract. Advances in understanding mechanisms of immune effector cell recruitment, antifungal effector mechanisms, and how the dynamic host-fungal interaction alters the local microenvironment to effect outcomes are highlighted. These advances illustrate exciting new therapeutic opportunities, but also emphasize the importance of understanding each unique fungus-host interaction for improving patient outcomes.

Ibrutinib‐associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non‐Hodgkin lymphoma: An observational study

“…35 Chamilos et al proposed there may be a "net state of immunosuppression" which includes factors affecting the adaptive and innate immune system, disease-related factors, ageing, comorbidities, exposure to fungal conidia, immunosuppressive drugs and possibly a genetic predisposition as contributing to ibrutinib-associated IFD. 15,31,36,37 The majority (71%) of patients in this survey had at least one predisposing factor linked with IFD, and frequently multiple risk factors were present. Future studies of IFD should probably concentrate on the host, rather than on the organism.…”

“…Other potential contributors include multiple prior treatments, diabetes mellitus, liver disease and for CLL patients—neutropenia, prior IFD, lymphopenia, stage, genetic abnormalities (eg aberrations of the TP53 or ATM genes or trisomy 12) and IgHV mutational status . Chamilos et al proposed there may be a “net state of immunosuppression” which includes factors affecting the adaptive and innate immune system, disease‐related factors, ageing, comorbidities, exposure to fungal conidia, immunosuppressive drugs and possibly a genetic predisposition as contributing to ibrutinib‐associated IFD . The majority (71%) of patients in this survey had at least one predisposing factor linked with IFD, and frequently multiple risk factors were present.…”

“…The majority (71%) of patients in this survey had at least one predisposing factor linked with IFD, and frequently multiple risk factors were present. Future studies of IFD should probably concentrate on the host, rather than on the organism …”

Interleukin 1α Is Critical for Resistance against Highly Virulent Aspergillus fumigatus Isolates

“…If this primary barrier is bypassed, airway epithelial cells and lung-resident macrophages comprise the first line of defense against inhaled conidia, while neutrophils and inflammatory monocytes are then sequentially recruited to the site to prevent fungal growth (16,17). Defining the immunological events that are necessary for A. fumigatus conidia to be cleared from the lungs without excessive and immune-mediated lung damage is a critical step toward understanding how the response is altered in different immunocompromised populations.…”

Immune responses to Mucorales growth forms: Do we know everything?

“…and Aspergillus spp have been well studied and reviewed. 2,3 By comparison, much less is known about the immune responses against members of Mucorales order. 4 Both mononuclear and polymorphonuclear phagocytes (PMNs) have the capacity to destroy fungal forms by the generation of toxic metabolites, fungicidal peptides and proteases.…”