Filifactor alocis Infection and Inflammatory Responses in the Mouse Subcutaneous Chamber Model

Abstract

dRecent microbiome studies have implicated a role for Filifactor alocis in periodontal disease. In this study, we investigated the colonization and survival properties of F. alocis in a mouse subcutaneous chamber model of infection and characterized host innate immune responses. An infection of 10 9 F. alocis successfully colonized all chambers; however, the infection was cleared after 72 h. F. alocis elicited a local inflammatory response with neutrophils recruited into the chambers at 2 h postinfection along with an increase in levels of the proinflammatory cytokines interleukin 1␤ (IL-1␤), IL-6, and tumor necrosis factor (TNF). F. alocis also induced apoptosis in chamber epithelial cells and neutrophils. Consistent with resolution of infection, neutrophil numbers and cytokine levels returned to baseline by 72 h. Fluorescent in situ hybridization (FISH) and quantitative PCR demonstrated that F. alocis exited the chambers and spread to the spleen, liver, lung, and kidney. Massive neutrophil infiltration was observed in the spleen and lungs, and the recruited neutrophils were in close proximity to the infecting bacteria. Significant epithelial injury was observed in the kidneys. Infection of all tissues was resolved after 7 days. This first in vivo study of the pathogenicity of F. alocis shows that in the chamber model the organism can establish a proinflammatory, proapoptotic local infection which is rapidly resolved by the host concordant with neutrophil influx. Moreover, F. alocis can spread to, and transiently infect, remote tissues where neutrophils can also be recruited.

Porphyromonas gingivalis infection in gestational diabetes mellitus and survival in tobacco smokers.

“…The rpoN gene (PGN_1202, 33277; PG1105, W83 orthologue; PGTDC60_1103, TDC60 orthologue), for example, encodes the alternative sigma factor, σ 54 . Bacteroides spp.…”

“…In a mouse model, it has been shown that T. denticola has an ability to disseminate to distant sites from the site of infection [246]. In a mouse subcutaneous model, it has been shown that the newly emerging periodontal pathogen, F. alocis has the ability to colonize and spread to distant sites [54].…”

“…Increased systemic inflammation has been suggested to be related to pregnancy complications, such as preeclampsia [54,270], with elevated levels of the acute phase protein, C-reactive protein (CRP), reported to be an effective early biomarker for GDM [271]. All women were recruited during the third semester, the stage of pregnancy when CRP levels have been reported to be highest in those with GDM [237].…”

“…F. alocis is relatively resistant to oxidative stress and possesses several virulence factors, such as sialoglycoproteins, proteases, adhesion molecules, neutrophil-activating protein A, and a calcium-binding acid repeat protein [31]. F. alocis can stimulate the production of host proinflammatory cytokines IL-1β, IL-6, and TNF, which in turn can stimulate pathways that activate osteoclasts and increase alveolar bone resorption [53,54]. F. alocis can also interact with other oral bacteria and form biofilms [55].…”

“…Furthermore, poor glycemic control has been reported to result in increased subgingival infection with these same two pathogens [230]. Increased low-grade systemic inflammation has been suggested to be related to pregnancy complications, such as preeclampsia [54,270], with elevated levels of the acute phase protein, C-reactive protein (CRP), suggested to be an effective early biomarker for GDM [271].…”