AUTHOR=Surendar Jayagopi , Hackenberg Roslind K. , Schmitt-Sánchez Fabio , Ossendorff Robert , Welle Kristian , Stoffel-Wagner Birgit , Sage Peter T. , Burger Christof , Wirtz Dieter C. , Strauss Andreas C. , Schildberg Frank A. TITLE=Osteomyelitis is associated with increased anti-inflammatory response and immune exhaustion JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1396592 DOI=10.3389/fimmu.2024.1396592 ISSN=1664-3224 ABSTRACT=Introduction

Osteomyelitis (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.

Methods

Using high-dimensional flow cytometry, we investigated the detailed innate and adaptive systemic immune cell populations in OMS and age- and sex-matched controls.

Results

Our 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.

Discussion

We 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.