MelLec Exacerbates the Pathogenesis of Aspergillus fumigatus-Induced Allergic Inflammation in Mice

Kazuya Tone, Mark H.T. Stappers, Remi Hatinguais, Ivy M. Dambuza, Fabián Salazar, Carol Wallace, Raif Yuecel, Petruta L. Morvay, Kazuyoshi Kuwano, Janet A. Willment, Gordon D. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Environmental factors, particularly fungi, influence the pathogenesis of allergic airway inflammation, but the mechanisms underlying these effects are still unclear. Melanin is one fungal component which is thought to modulate pulmonary inflammation. We recently identified a novel C-type lectin receptor, MelLec (Clec1a), which recognizes fungal 1,8-dihydroxynaphthalene (DHN)-melanin and is able to regulate inflammatory responses. Here we show that MelLec promotes pulmonary allergic inflammation and drives the development of Th17 T-cells in response to spores of Aspergillus fumigatus. Unexpectedly, we found that MelLec deficiency was protective, with MelLec-/- animals showing normal weight gain and significantly reduced pulmonary inflammation in our allergic model. The lungs of treated MelLec-/- mice displayed significantly reduced inflammatory foci and reduced bronchial wall thickening, which correlated with a reduced cellular influx (particularly neutrophils and inflammatory monocytes) and levels of inflammatory cytokines and chemokines. Notably, fungal burdens were increased in MelLec-/- animals, without apparent adverse effects, and there were no alterations in the survival of these mice. Characterization of the pulmonary T-cell populations, revealed a significant reduction in Th17 cells, and no alterations in Th2, Th1 or Treg cells. Thus, our data reveal that while MelLec is required to control pulmonary fungal burden, the inflammatory responses mediated by this receptor negatively impact the animal welfare in this allergic model.
Original languageEnglish
Article number675702
Number of pages7
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 28 May 2021

Keywords

  • allergy
  • Aspergillus fumigatus
  • asthma
  • C-type lectin
  • MelLec

Fingerprint

Dive into the research topics of 'MelLec Exacerbates the Pathogenesis of Aspergillus fumigatus-Induced Allergic Inflammation in Mice'. Together they form a unique fingerprint.

Cite this