Abstract
Invasive pulmonary aspergillosis is a frequent complication in immunocompromised individuals, and it continues to be an important cause of mortality in patients undergoing hematopoietic stem cell transplantation. In addition to antifungal therapy used for mycoses, immune-modulatory molecules such as cytokines and chemokines can modify the host immune response and exhibit a promising form of antimicrobial therapeutics to combat invasive fungal diseases. Cytokine and chemokine profiles may also be applied as biomarkers during fungal infections and clinical research has demonstrated different activation patterns of cytokines in invasive mycoses such as aspergillosis. In this review, we summarize different aspects of cytokines that have been described to date and provide possible future directions in research on invasive pulmonary aspergillosis following hematopoietic stem cell transplantation. These findings suggest that cytokines and chemokines may serve as useful biomarkers to improve diagnosis and monitoring of infection.
Highlights
The significant increase of both the pro-inflammatory cytokine TNF-α and chemoattraction chemokines IL-8, chemokine ligand (CCL)-20, and CXCL10 were observed with stimulation by the Aspergillus antigen 18-kDa RNase Aspf1 [26], compared to the levels expressed by unstimulated dendritic cells (DCs)
Natural killer (NK) cells are lymphoid cells in peripheral blood that play a critical role in the innate host defense and their cell numbers are related to the severity of invasive pulmonary aspergillosis (IPA) [24]
The expression of in vitro and in vivo cytokines/chemokines varies in the different studies, these discrepancies may be explained by differences in cell types responding to Aspergillus stimuli and the different patient populations
Summary
Fungi are among the most extensively distributed microorganisms and are ubiquitous in the environment. The Toll-like receptor (TLR) family, one of the PRRs directed against conserved molecules in pathogens, plays a major role in the recognition of Aspergillus These aspergillosis-related TLRs include TLR-2, TLR-4, and TLR9 [10,11]. These TLRs potentially induce the production of pro-inflammatory cytokines and reactive oxygen species (ROS) through a MyD88-NF-κB-dependent signaling pathway [12]. In addition to these MyD88-dependent processes in macrophage-mediated responses, the uptake of A. fumigatus spores by respiratory epithelia plays a crucial role in either fungal killing the fungus or containing the organisms within the airway epithelial cells’ (AECs) phagosome [13]. The complex cytokine and chemokine behaviors produced in response to IA have provided crucial insights into the pathogenesis of IA, and the tracking of changes in these molecules may potentially help guide clinicians in decisions regarding the prophylaxis for and treatment of aspergillosis, especially in HSCT patients
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