Frontiers in Immunology (Apr 2024)

Osteomyelitis is associated with increased anti-inflammatory response and immune exhaustion

  • Jayagopi Surendar,
  • Roslind K. Hackenberg,
  • Roslind K. Hackenberg,
  • Fabio Schmitt-Sánchez,
  • Robert Ossendorff,
  • Kristian Welle,
  • Birgit Stoffel-Wagner,
  • Peter T. Sage,
  • Christof Burger,
  • Dieter C. Wirtz,
  • Andreas C. Strauss,
  • Frank A. Schildberg

DOI
https://doi.org/10.3389/fimmu.2024.1396592
Journal volume & issue
Vol. 15

Abstract

Read online

IntroductionOsteomyelitis (OMS) is a bone infection causing bone pain and severe complications. A balanced immune response is critical to eradicate infection without harming the host, yet pathogens manipulate immunity to establish a chronic infection. Understanding OMS-driven inflammation is essential for disease management, but comprehensive data on immune profiles and immune cell activation during OMS are lacking.MethodsUsing high-dimensional flow cytometry, we investigated the detailed innate and adaptive systemic immune cell populations in OMS and age- and sex-matched controls.ResultsOur study revealed that OMS is associated with increased levels of immune regulatory cells, namely T regulatory cells, B regulatory cells, and T follicular regulatory cells. In addition, the expression of immune activation markers HLA-DR and CD86 was decreased in OMS, while the expression of immune exhaustion markers TIM-3, PD-1, PD-L1, and VISTA was increased. Members of the T follicular helper (Tfh) cell family as well as classical and typical memory B cells were significantly increased in OMS individuals. We also found a strong correlation between memory B cells and Tfh cells.DiscussionWe conclude that OMS skews the host immune system towards the immunomodulatory arm and that the Tfh memory B cell axis is evident in OMS. Therefore, immune-directed therapies may be a promising alternative for eradication and recurrence of infection in OMS, particularly in individuals and areas where antibiotic resistance is a major concern.

Keywords