| First Author | Ding S | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 3 | Pages | 102192 |
| PubMed ID | 33718841 | Mgi Jnum | J:314713 |
| Mgi Id | MGI:6827348 | Doi | 10.1016/j.isci.2021.102192 |
| Citation | Ding S, et al. (2021) Interactions between fungal hyaluronic acid and host CD44 promote internalization by recruiting host autophagy proteins to forming phagosomes. iScience 24(3):102192 |
| abstractText | 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 Ca(2+) concentrations and activates CaMKKbeta and its downstream target AMPKalpha, 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. |
