Traditionally, the innate immune system—the body’s first line of defence—was thought to lack the ability to “remember” past threats. Unlike the adaptive immune system, which can recognize and attack pathogens it has previously encountered, innate immunity was viewed as a more generalized, short-term response.
However, over the past decade, research has challenged this notion. Scientists have shown that innate immune cells can develop a form of immunological memory—a phenomenon now known as trained innate immunity or TRIM. This “training” can boost responses to infections and has even shown promise in anti-cancer studies.
But this heightened state of readiness isn’t always beneficial. Inflammation, while protective in many contexts, can exacerbate diseases if it’s not tightly controlled.
Harnessing the immune system has long been at the forefront of medical research, from vaccines to immunotherapies designed to treat cancer and autoimmune diseases. Now, scientists have made a key discovery: training the innate immune system can sometimes exacerbate bone loss in chronic inflammatory diseases like periodontitis and arthritis (Figure 1).
Figure 1: Graphical abstract.
The team sought to understand how TRIM influences inflammatory diseases that involve bone loss. They used β-glucan, a compound found in fungi, to induce TRIM in experimental models of periodontitis and arthritis. The goal was to observe how this trained immune state would affect osteoclast precursors—cells that develop into osteoclasts, the bone-resorbing cells responsible for breaking down bone tissue.
The researchers found that β-glucan primed these precursors, making them more likely to differentiate into osteoclasts when faced with an inflammatory challenge. This increased the potential for bone loss in the presence of conditions like periodontitis or arthritis.
Importantly, the study clarified that TRIM doesn’t directly cause bone loss on its own. Instead, it sets the stage for an amplified response if a second inflammatory trigger is introduced.
The research adds complexity to our understanding of TRIM. While earlier studies have shown that training the innate immune system with agents like β-glucan can have beneficial effects—such as fighting tumours—this study demonstrates that context is critical.
The same immune training that helps fight cancer could, under different circumstances, worsen chronic inflammatory diseases. While trained innate immunity holds great promise for boosting defences against infections and cancer, it also has the potential to worsen inflammatory diseases like arthritis and periodontitis. This new research highlights the need for careful consideration when designing immune-based therapies.
Journal article: Haacke, N., et al. 2025. Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice. Developmental Cell.
Summary by Stefan Botha
