Shengli Ding, Jing Yang, Xuehuan Feng, Aseem Pandey, Rola Barhoumi, Dongmei Zhang, Samantha L Bell, Yue Liu, Luciana Fachini da Costa, Allison Rice-Ficht, Robert O Watson, Kristin L Patrick, Qing-Ming Qin, Thomas A Ficht, Paul de Figueiredo
iScience 2021 Mar 19Phagocytosis 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. © 2021 The Authors.
Shengli Ding, Jing Yang, Xuehuan Feng, Aseem Pandey, Rola Barhoumi, Dongmei Zhang, Samantha L Bell, Yue Liu, Luciana Fachini da Costa, Allison Rice-Ficht, Robert O Watson, Kristin L Patrick, Qing-Ming Qin, Thomas A Ficht, Paul de Figueiredo. Interactions between fungal hyaluronic acid and host CD44 promote internalization by recruiting host autophagy proteins to forming phagosomes. iScience. 2021 Mar 19;24(3):102192
PMID: 33718841
View Full Text