Binding of Pneumocystis carinii to the lung epithelial cell receptor HSPA5 (GRP78)

Theodore J Kottom1, Deanne M Hebrink1, Andrew H Limper1

  • 1From the Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

Insights

Researchers identified heat shock protein 5 (HSPA5) as a key receptor mediating Pneumocystis attachment to lung epithelial cells. This discovery offers new insights into Pneumocystis lung colonization mechanisms.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Lung macrophages are crucial in Pneumocystis-host interactions.
  • Initial binding and colonization of airway epithelium by Pneumocystis remain poorly understood.
  • Previous studies noted cell-signaling events after organism binding but lacked receptor identification.

Purpose of the Study:

  • To identify the host receptors involved in Pneumocystis attachment to lung surfaces.
  • To investigate the role of heat shock protein 5 (HSPA5) in Pneumocystis lung colonization.

Main Methods:

  • Affinity chromatography was employed to identify potential host receptors.
  • Experiments utilized a rat lung epithelial cell line and primary rat airway epithelial cells (AECs).
  • CHO1 cells overexpressing HSPA5 were used to validate the interaction.

Main Results:

  • Heat shock protein 5 (HSPA5), also known as GRP78, was identified as a potential host receptor.
  • Pneumocystis carinii (Pc) organisms demonstrated binding to HSPA5 on both epithelial cell lines and primary AECs.
  • Pc exhibited increased binding to CHO1 cells overexpressing HSPA5, confirming a Pc-HSPA5 interaction.

Conclusions:

  • HSPA5 plays a significant role in mediating the attachment of Pneumocystis to host lung epithelium.
  • This finding provides novel insights into the initial stages of Pneumocystis lung colonization.
  • The identified Pc-HSPA5 interaction is a critical factor in Pneumocystis-host lung epithelium engagement.

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