Immune and regulatory functions of neutrophils in inflammatory bone loss

Abstract

Although historically viewed as merely anti-microbial effectors in acute infection or injury, neutrophils are now appreciated to be functionally versatile with critical roles also in chronic inflammation. Periodontitis, a chronic inflammatory disease that destroys the tooth-supporting gums and bone, is particularly affected by alterations in neutrophil numbers or function, as revealed by observations in monogenic disorders and relevant mouse models. Besides being a significant debilitating disease and health burden in its own right, periodontitis is thus an attractive model to dissect uncharted neutrophil-associated (patho)physiological pathways. Here, we summarize recent evidence that neutrophils can contribute to inflammatory bone loss not only through the typical bystander injury dogma but intriguingly also through their absence from the affected tissue, where they normally perform important immunomodulatory functions. Moreover, we discuss recent advances in the interactions of neutrophils with the vascular endothelium and – upon extravasation – with bacteria, and how the dysregulation of these interactions leads to inflammatory tissue damage. Overall, neutrophils have both protective and destructive roles in periodontitis, as they are involved in both the maintenance of periodontal tissue homeostasis and the induction of inflammatory bone loss. This highlights the importance of developing approaches that promote or sustain a fine balance between homeostatic immunity and inflammatory pathology.

Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1

“…2 Whether the immunopathologic consequences of tissue neutropenia in LAD1 are replicated in other forms of neutropenia remains to be seen.…”

“…1 The mucocutaneous lesions in LAD1 were widely assumed to be due to infections that were a result of the relative tissue neutropenia caused by the inability of LAD1 neutrophils to enter the tissue and control microbes. 2 However, recent work has shown that LAD1-associated oral disease is actually a microbe-induced hyperinflammatory response. 3,4 …”

Filifactor alocis Promotes Neutrophil Degranulation and Chemotactic Activity

“…Furthermore, congenital diseases, such as leukocyte adhesion deficiency, that impair neutrophil chemotaxis result in severe peri- odontitis at an early stage in life (46,47). In the mouse subcutaneous chamber model of infection, the newly appreciated periodontal pathogen F. alocis elicits a local inflammatory response with extensive neutrophil recruitment as well as spread to remote tissues, inducing lung edema with neutrophil recruitment and causing acute kidney injury (10).…”

Signature of Microbial Dysbiosis in Periodontitis

“…CP does not result from individual pathogens but rather from polymicrobial synergy and dysbiosis (4) associated with a dysregulated immune response inducing inflammation-mediated tissue damage (5). Host genetic components have also been implicated in CP, with multiple genes contributing cumulatively to the host's overall disease risk (or protection) through effects on the host immune response and the microbiome (6). Since the Human Microbiome Project (HMP) (7), microbiota have been analyzed based on partial sequencing of the 16S rRNA gene, with different numbers of healthy and CP samples.…”