Surfactant protein A (SP-A) is a multifunctional host defense collectin that was first identified as a component of pulmonary surfactant. Although SP-A is also expressed in various tissues, including the urinary tract, its innate immune functions in nonpulmonary tissues are poorly understood. In this study, we demonstrated that adherence of uropathogenic Escherichia coli (UPEC) to the bladder was enhanced in SP-A–deficient mice, which suggests that SP-A plays an important role in innate immunity against UPEC. To understand the innate immune functions of SP-A in detail, we performed in vitro experiments. SP-A directly bound to UPEC in a Ca2+-dependent manner, but it did not agglutinate UPEC. Our results suggest that a bouquet-like arrangement seems unsuitable to agglutinate UPEC. Meanwhile, SP-A inhibited growth of UPEC in human urine. Furthermore, the binding of SP-A to UPEC decreased the adherence of bacteria to urothelial cells. These results indicate that direct action of SP-A on UPEC is important in host defense against UPEC. Additionally, adhesion of UPEC to urothelial cells was decreased when the cells were preincubated with SP-A. Adhesion of UPEC to urothelial cells is achieved via interaction between FimH, an adhesin located at bacterial pili, and uroplakin Ia, a glycoprotein expressed on the urothelium. SP-A directly bound to uroplakin Ia and competed with FimH for uroplakin Ia binding. These results lead us to conclude that SP-A plays important roles in host defense against UPEC.
This work was supported by Japan Society for the Promotion of Science KAKENHI Grant 26861278 (to J.H.).
Abbreviations used in this article:
- A/D chimera
- chimeric protein of surfactant protein A and surfactant protein D
- bacterial alkaline phosphatase
- enhanced GFP
- FimH receptor-binding domain
- surfactant protein A
- surfactant protein D
- uropathogenic Escherichia coli
- urinary tract infection
- Received December 18, 2015.
- Accepted January 30, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.