GRP78 and Integrins Play Different Roles in Host Cell Invasion during Mucormycosis
Abstrak
Mucormycosis caused by Rhizopus species is a fungal infection with often fatal prognosis. Inhalation of spores is the major route of entry, with nasal and alveolar epithelial cells among the first cells that encounter the fungi. In patients with hematologic malignancies or those undergoing cytotoxic chemotherapy, Rhizopus causes pulmonary infections. On the other hand, DKA patients predominantly suffer from rhinoorbital/cerebral mucormycosis. The reason for such disparity in disease types by the same fungus is not known. Here, we show that the unique susceptibility of DKA subjects to rhinoorbital/cerebral mucormycosis is likely due to specific interaction between nasal epithelial cell GRP78 and fungal CotH3, the expression of which increases in the presence of host factors present in DKA. In contrast, pulmonary mucormycosis is initiated via interaction of inhaled spores expressing CotH7 with integrin β1 receptor, which activates EGFR to induce fungal invasion of host cells. These results introduce a plausible explanation for disparate disease manifestations in DKA versus those in hematologic malignancy patients and provide a foundation for development of therapeutic interventions against these lethal forms of mucormycosis.
Penulis (11)
Abdullah Alqarihi
Teclegiorgis Gebremariam
Yiyou Gu
Marc Swidergall
Sondus Alkhazraji
Sameh S. M. Soliman
Vincent M. Bruno
John E. Edwards
Scott G. Filler
Priya Uppuluri
Ashraf S. Ibrahim
Akses Cepat
- Tahun Terbit
- 2020
- Bahasa
- en
- Total Sitasi
- 106×
- Sumber Database
- CrossRef
- DOI
- 10.1128/mbio.01087-20
- Akses
- Open Access ✓