Surface Glycans Regulate Salmonella Infection-Dependent Directional Switch in Macrophage Galvanotaxis Independent of NanH
Abstract
Salmonellainvades and disrupts gut epithelium integrity, creating an infection-generated electric field that can drive directional migration of macrophages, a process called galvanotaxis. Phagocytosis of bacteria reverses the direction of macrophage galvanotaxis, implicating a bioelectrical mechanism to initiate life-threatening disseminations. The force that drives direction reversal of macrophage galvanotaxis is not understood. One hypothesis is thatSalmonellacan alter the electrical properties of the macrophages by modifying host cell surface glycan composition, which is supported by the fact that cleavage of surface-exposed sialic acids with a bacterial neuraminidase severely impairs macrophage galvanotaxis, as well as phagocytosis. Here, we utilize N-glycan profiling by nanoLC-chip QTOF mass cytometry to characterize the bacterial neuraminidase-associated compositional shift of the macrophage glycocalyx, which revealed a decrease in sialylated and an increase in fucosylated and high mannose structures. TheSalmonellananHgene, encoding a putative neuraminidase, is required for invasion and internalization in a human colonic epithelial cell infection model. To determine whether NanH is required for theSalmonellainfection-dependent direction reversal, we constructed and characterized ananHdeletion mutant and found that NanH is partially required forSalmonellainfection in primary murine macrophages. However, compared to wild typeSalmonella, infection with thenanHmutant only marginally reduced the cathode-oriented macrophage galvonotaxis, without canceling direction reversal. Together, these findings strongly suggest that while neuraminidase-mediated N-glycan modification impaired both macrophage phagocytosis and galvanotaxis, yet to be defined mechanisms other than NanH may play a more important role in bioelectrical control of macrophage trafficking, which potentially triggers dissemination.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 25, 2022
- Source ID
- 10.1128/iai.00516-21
Entities
People
- B. P. Guo
- B. Reid
- C. B. Lebrilla
- E. Maverakis
- G. Luxardi
- Gaofeng Xu
- K. Zhu
- Minghui Zhao
- Yao-Hui Sun
Organizations
- National Institutes of Health
- University of California
- University of California, Davis