Interleukin‐34 permits Porphyromonas gingivalis survival and NF‐κB p65 inhibition in macrophages

Abstract

Interleukin‐34 (IL‐34) is a cytokine that supports the viability and differentiation of macrophages. An important cytokine for the development of epidermal immunity, IL‐34, is present and plays a role in the immunity of the oral environment. IL‐34 has been linked to inflammatory periodontal diseases, which involve innate phagocytes, including macrophages. Whether IL‐34 can alter the ability of macrophages to effectively interact with oral microbes is currently unclear. Using macrophages derived from human blood monocytes with either the canonical cytokine colony‐stimulating factor (CSF)1 or IL‐34, we compared the ability of the macrophages to phagocytose, kill, and respond through the production of cytokines to the periodontal keystone pathogen Porphyromonas gingivalis. While macrophages derived from both cytokines were able to engulf the bacterium equally, IL‐34‐derived macrophages were much less capable of killing internalized P. gingivalis. Of the macrophage cell surface receptors known to interact with P. gingivalis, dendritic cell‐specific intercellular adhesion molecule‐grabbing nonintegrin was found to have the largest variation between IL‐34‐ and CSF1‐derived macrophages. We also found that upon interaction with P. gingivalis, IL‐34‐derived macrophages produced significantly less of the neutrophil chemotactic factor IL‐8 than macrophages derived in the presence of CSF1. Mechanistically, we identified that the levels of IL‐8 corresponded with P. gingivalis survival and dephosphorylation of the major transcription factor NF‐κB p65. Overall, we found that macrophages differentiated in the presence of IL‐34, a dominant cytokine in the oral gingiva, have a reduced ability to kill the keystone pathogen P. gingivalis and may be susceptible to specific bacteria‐mediated cytokine modification.

The changes and potential effects of zinc homeostasis in periodontitis microenvironment

“…When P. gingivalis attacks, innate immune cells, including neutrophils and macrophages, are recruited to the local tissue as the first line of the host immune defense system and eliminate the invading pathogens through phagocytosis and further varieties of pathogen‐killing mechanisms (Almarghlani et al, 2022; Cekici et al, 2014). The clearance of invading P. gingivalis by neutrophils involves a series of functions, such as neutrophils adhesion and chemotaxis, phagocytosis of pathogens, and pathogen killing mechanisms, including nicotinamide adenine dinucleotide phosphate (NADPH, NOX)‐dependent respiratory burst function, and the formation of NETs (Chen, Tong, et al, 2022; Gu et al, 2020; Liu et al, 2021; Mikolai et al, 2020; Raad et al, 2019).…”

Identification of potential diagnostic biomarkers associated with periodontitis by comprehensive bioinformatics analysis

“…IL-8 is continuously expressed in periodontal tissues and mediates the recruitment of neutrophils to gingival tissues 26 . Studies have reported that IL-8 expression is significantly increased in periodontal disease and is associated with the occurrence of periodontitis 27 , 28 . Moritz et al demonstrated that as the severity of periodontal lesions increases, neutrophil recruitment mediated by CXCL6 can supplement the recruitment pathway of IL-8 21 .…”

The oral-gut-circulatory axis: from homeostasis to colon cancer

“…The other primary fimbriae, known as FimA, is a TLR2 agonist targets thereby inhibit the autophagic degradation of P. gingivalis, which may also facilitate its dissemination to distant sites within DCs (El-Awady et al, 2015). Furthermore, another investigation revealed that macrophages subjected to differentiation in the presence of IL-34, a predominant cytokine in the oral gingival environment, exhibit significantly diminished capacity to eliminate engulfed P. gingivalis (Almarghlani et al, 2022). In conclusion, P. gingivalis exhibits a remarkable capacity to evade immune defenses and establish persistence within diverse cell types, notably DCs and macrophages.…”