Cytokine profiling of pulmonary aspergillosis
Open accessAbstract
Summary: Aspergillus fumigatus is ubiquitous and yet causes invasive, chronic and allergic disease of the lung. Chronic cavitary pulmonary aspergillosis (CCPA) is a slowly destructive form of pulmonary aspergillosis, without immunocompromise. We hypothesized that CCPA cytokine gene polymorphisms would differ from patients with allergic bronchopulmonary aspergillosis (ABPA) and uninfected controls. We have profiled functional cytokine gene polymorphisms for interleukin (IL)‐10, IL‐15, transforming growth factors (TGF)‐β1, tumour necrosis factor (TNF)‐α and interferon (IFN)‐γ in patients with CCPA (n = 24) who were compared with other forms of aspergillosis (mostly ABPA) (n = 15) and with ethnically matched controls (n = 65–330). Results are described with reference to the high‐producing genotype in each case. Susceptibility to aspergillosis (all patients compared with normal controls) was associated with higher frequency of the IL‐15 +13689*A allele (OR = 2.37, P = 0.0028) and A/A genotype (χ 2 = 10.31, P < 0.001), with a lower frequency of the TNF‐α−308*A/A genotype (χ 2 = 11.05, P < 0.01). Within the aspergillosis patients, CCPA is associated with lower frequency of the IL‐10 −1082*G allele (OR = 0.38, P = 0.0006) and G/G genotype (χ 2 = 22.45, P < 0.001) and with a lower frequency of the TGF‐β1 +869 *T allele (OR +0.42, P < 0.0029) and T/T genotype (χ 2 = 17.82, P < 0.001) compared with non‐CCPA patients and normal controls. Patients infected with Aspergillus appear to be higher producers of IL‐15, a Th2‐promoting cytokine, and lower producers of TNF‐α, a cytokine central in protective responses. CCPA occurs in patients who are genetically lower producers of both IL‐10 and TGF‐β1. As these cytokines are regulatory and anti‐inflammatory, CCPA may be a consequence of poor inflammatory response control in the lung.
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Polymorphisms in several cytokines are associated with susceptibility to specific fungal diseases: aspergillosis with IL-1, IL-10, IL-15, and IL-23; candidiasis with IL-4; paracoccidioidomycosis with IL-4; and blastomycosis with IL-6.
“polymorphisms in a number of cytokines have also been found to predispose to fungal disease: aspergillosis (IL-1 [30], IL-10 [31,32], IL-15 [32], and IL-23); candidiasis (IL-4) [33,34]; paracoccidioidomycosis (IL-4) [35]; and blastomycosis (IL-6) [36].”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [32]
Polymorphisms within the tumor necrosis factor-alpha gene and its receptors are associated with susceptibility to aspergillosis.
“Polymorphisms within the tumor necrosis factor-α (TNF-α) gene [32] and its receptors [37,38] have also been associated with susceptibility to aspergillosis.”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [32]
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- Authors
- Sambatakou, H., Pravica, V., Hutchinson, I. V., & Denning, D. W.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- University of Manchester (GB)
- Corresponding author
- Denning, D. W.
- Venue
- International Journal of Immunogenetics
- Publisher
- Wiley
- Published
- 2006-07-18
- Volume
- 33
- Issue
- 4
- Pages
- 297-302
- ISSN
- 1744-3121 (ISSN-L)
- 1744-313X
- OpenAlex
- W2095369042
- Cited by
- 83
- References
- 39
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 7 · 2013: 4 · 2012: 6
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Immunogenetics (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- chronic cavitary pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, Aspergillus fumigatus, cytokine gene polymorphisms, IL-15, IL-10, TNF-α, TGF-β1, interferon-gamma, genetic susceptibility, Th2 cytokines, Th1 cytokines
- MeSH terms
- Adult, Aspergillosis, Aspergillosis, Allergic Bronchopulmonary, Aspergillus fumigatus, England, Genotype, Humans, Interferon-gamma, Lung Diseases, Fungal, Middle Aged, Sinusitis, Tumor Necrosis Factor-alpha, Case-Control Studies, Polymerase Chain Reaction, Cytokines, Transforming Growth Factor beta, Interleukin-10, Interleukin-15, Genetic Predisposition to Disease, Transforming Growth Factor beta1
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