Characterizing the Mechanisms of Nonopsonic Uptake of Cryptococci by Macrophages

Research output: Contribution to journalArticle

Authors

  • Jenson Lim
  • Christopher J. Coates
  • Paula I. Seoane
  • Mariam Garelnabi
  • Pauline Monteith
  • Camille L Macleod
  • Claire J Escaron
  • Gordon D Brown

Colleges, School and Institutes

External organisations

  • Biological and Environmental Sciences, University of Stirling
  • Department of Biosciences, College of Science, Swansea University
  • Biological and Environmental Sciences, University of Stirling

Abstract

The pathogenic fungus Cryptococcus enters the human host via inhalation into the lung and is able to reside in a niche environment that is serum- (opsonin) limiting. Little is known about the mechanism by which nonopsonic phagocytosis occurs via phagocytes in such situations. Using a combination of soluble inhibitors of phagocytic receptors and macrophages derived from knockout mice and human volunteers, we show that uptake of nonopsonized Cryptococcus neoformans and C. gattii via the mannose receptor is dependent on macrophage activation by cytokines. However, although uptake of C. neoformans is via both dectin-1 and dectin-2, C. gattii uptake occurs largely via dectin-1. Interestingly, dectin inhibitors also blocked phagocytosis of unopsonized Cryptococci in wax moth (Galleria mellonella) larvae and partially protected the larvae from infection by both fungi, supporting a key role for host phagocytes in augmenting early disease establishment. Finally, we demonstrated that internalization of nonopsonized Cryptococci is not accompanied by the nuclear translocation of NF-κB or its concomitant production of proinflammatory cytokines such as TNF-α. Thus, nonopsonized Cryptococci are recognized by mammalian phagocytes in a manner that minimizes proinflammatory cytokine production and potentially facilitates fungal pathogenesis.

Details

Original languageEnglish
Pages (from-to)3539-3546
JournalJournal of Immunology
Volume200
Issue number9
Early online date11 Apr 2018
Publication statusPublished - 15 May 2018

Keywords

  • Journal Article