The metabolic cytokine adiponectin inhibits inflammatory lung pathology in invasive aspergillosis

Nansalmaa Amarsaikhan, Angar Tsoggerel, Christopher Hug, Steven Templeton

Research output: Contribution to journalArticle

Abstract

Systemic immunity and metabolism are coregulated by soluble factors, including the insulin-regulating adipose tissue cytokine adiponectin. How these factors impact detrimental inflammatory responses during fungal infection remains unknown. In this study, we observed that mortality, fungal burden, and tissue histopathology were increased in adiponectin-deficient mice in a neutropenic model of invasive aspergillosis. Lung RNA sequencing, quantitative RT-PCR, and subsequent pathway analysis demonstrated activation of inflammatory cytokine pathways with upstream regulation by IL-1 and TNF in adiponectin-deficient mice with decreased/inhibited anti-inflammatory genes/pathways, suggesting broad cytokine-mediated pathology along with ineffective fungal clearance. Quantitative RT-PCR analysis confirmed increased transcription of IL-1a, IL-6, IL-12b, IL-17A/F, and TNF in adiponectin-deficient mice at early time points postinfection, with a specific increase in intracellular TNF in alveolar macrophages. Although eosinophil recruitment and activation were increased in adiponectin-deficient mice, mortality was delayed, but not decreased, in mice deficient in both adiponectin and eosinophils. Interestingly, neutrophil depletion was required for increased inflammation in adiponectin-deficient mice in response to swollen/fixed conidia, suggesting that immune suppression enhances detrimental inflammation, whereas invasive fungal growth is dispensable. Our results suggest that adiponectin inhibits excessive lung inflammation in invasive aspergillosis. Our study has therefore identified the adiponectin pathway as a potential source for novel therapeutics in immune-compromised patients with detrimental immunity to invasive fungal infection.

Original languageEnglish (US)
Pages (from-to)956-963
Number of pages8
JournalJournal of Immunology
Volume203
Issue number4
DOIs
StatePublished - Aug 15 2019

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Aspergillosis
Adiponectin
Pathology
Cytokines
Lung
Eosinophils
Immunity
Inflammation
RNA Sequence Analysis
Activation Analysis
Polymerase Chain Reaction
Fungal Spores
Interleukin-17
Mortality
Mycoses
Alveolar Macrophages
Interleukin-1
Adipose Tissue
Interleukin-6
Pneumonia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The metabolic cytokine adiponectin inhibits inflammatory lung pathology in invasive aspergillosis. / Amarsaikhan, Nansalmaa; Tsoggerel, Angar; Hug, Christopher; Templeton, Steven.

In: Journal of Immunology, Vol. 203, No. 4, 15.08.2019, p. 956-963.

Research output: Contribution to journalArticle

Amarsaikhan, Nansalmaa ; Tsoggerel, Angar ; Hug, Christopher ; Templeton, Steven. / The metabolic cytokine adiponectin inhibits inflammatory lung pathology in invasive aspergillosis. In: Journal of Immunology. 2019 ; Vol. 203, No. 4. pp. 956-963.
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