Interactions between fungal hyaluronic acid and host CD44 promote internalization by recruiting host autophagy proteins to forming phagosomes. Academic Article uri icon

abstract

  • Phagocytosis and autophagy play critical roles in immune defense. The human fungal pathogen Cryptococcus neoformans (Cn) subverts host autophagy-initiation complex (AIC)-related proteins, to promote its phagocytosis and intracellular parasitism of host cells. The mechanisms by which the pathogen engages host AIC-related proteins remain obscure. Here, we show that the recruitment of host AIC proteins to forming phagosomes is dependent upon the activity of CD44, a host cell surface receptor that engages fungal hyaluronic acid (HA). This interaction elevates intracellular Ca2+ concentrations and activates CaMKKβ and its downstream target AMPKα, which results in activation of ULK1 and the recruitment of AIC components. Moreover, we demonstrate that HA-coated beads efficiently recruit AIC components to phagosomes and CD44 interacts with AIC components. Taken together, these findings show that fungal HA plays a critical role in directing the internalization and productive intracellular membrane trafficking of a fungal pathogen of global importance.

published proceedings

  • iScience

altmetric score

  • 0.25

author list (cited authors)

  • Ding, S., Yang, J., Feng, X., Pandey, A., Barhoumi, R., Zhang, D., ... de Figueiredo, P.

citation count

  • 2

complete list of authors

  • Ding, Shengli||Yang, Jing||Feng, Xuehuan||Pandey, Aseem||Barhoumi, Rola||Zhang, Dongmei||Bell, Samantha L||Liu, Yue||da Costa, Luciana Fachini||Rice-Ficht, Allison||Watson, Robert O||Patrick, Kristin L||Qin, Qing-Ming||Ficht, Thomas A||de Figueiredo, Paul

publication date

  • March 2021