Filifactor alocis Promotes Neutrophil Degranulation and Chemotactic Activity

Authors:
Publisher website
Google Scholar
Abstract
Filifactor alocisis a recently recognized periodontal pathogen; however, little is known regarding its interactions with the immune system. As the first-responder phagocytic cells, neutrophils are recruited in large numbers to the periodontal pocket, where they play a crucial role in the innate defense of the periodontium. Thus, in order to colonize, successful periodontal pathogens must devise means to interfere with neutrophil chemotaxis and activation. In this study, we assessed major neutrophil functions, including degranulation and cell migration, associated with the p38 mitogen-activated protein kinase (MAPK) signaling pathway upon challenge withF. alocis.Under conditions lacking a chemotactic gradient,F. alocis-challenged neutrophils had increased migration compared to uninfected cells, indicating thatF. alocisincreases chemokinesis in human neutrophils. In addition, neutrophil chemotaxis induced by interleukin-8 was significantly enhanced when cells were challenged withF. alocis, compared to noninfected cells. Similar to live bacteria, heat-killedF. alocisinduced both random and directed migration of human neutrophils. The interaction ofF. alociswith Toll-like receptor 2 induced granule exocytosis along with a transient ERK1/2 and sustained p38 MAPK activation. Moreover,F. alocis-induced secretory vesicle and specific granule exocytosis were p38 MAPK dependent. Blocking neutrophil degranulation with TAT-SNAP23 fusion protein significantly reduced the chemotactic and random migration induced byF. alocis. Therefore, we propose that induction of random migration byF. alociswill prolong neutrophil traffic time in the gingival tissue, and subsequent degranulation will contribute to tissue damage.
Funding Information
  • HHS | NIH | National Institute of Dental and Craniofacial Research (DE024509)
  • HHS | NIH | National Institute of Dental and Craniofacial Research (DE011111, DE012505, DE017921)

This publication has 62 references indexed in Scilit: