Grant: Project Grant

Tuberculosis (TB) is the leading infectious killer globally, causing around 1.5 million deaths each year. In Canada, TB disproportionately affects First Nations individuals, foreign-born individuals, and refugees, leading to severe impacts on these vulnerable populations. With the global population over 60 years old projected to more than triple by 2050, TB's impact on the elderly will become increasingly significant. Current TB vaccines and treatments are less effective in older adults due to age-related immune changes. Traditional vaccine approaches have primarily targeted T-cells, but aging impairs T-cell responses. Therefore, new strategies to protect the elderly are urgently needed. Recent research has shown that innate immune cells such as monocytes and macrophages, previously thought to lack memory, can develop memory-like responses known as Trained immunity, suggesting a new avenue for TB protection. However, innate immunity also undergoes age-related changes; therefore, understanding whether trained immunity can be induced in elderly hosts is critical for designing new interventions to combat TB. In the current proposal, we will elucidate the mechanism underlying the innate immune cell defect and identify whether trained immunity can restore their protective response.