Steven Templeton, Ph.D.

Institution: Indiana University

Project: Adiponectin-Mediated Inhibition of Detrimental Inflammation in Invasive Aspergillosis

Grant(s): Innovation Award

Many patients with chronic diseases that affect lung function may require a lung transplant. These patients receive long-term immune suppressive therapy to prevent organ rejection and manage detrimental inflammation. However, these drugs render patients susceptible to "opportunistic" lung infections, including fungal infections such as the highly fatal invasive aspergillosis (IA). Current drugs to treat IA are limited, drug resistance is increasing and residual immune responses may cause further lung damage. In our preliminary studies, we identified a novel protective role for the protein hormone adiponectin in IA. We will study adiponectin-mediated inhibition of detrimental inflammation in IA. In addition, we will assess the ability of a new adiponectin receptor-binding drug, AdipoRon, to dampen inflammation and improve survival in infected mice. Our proposed work will identify novel targets with therapeutic potential and open new avenues of research in the development of detrimental immunity to infection.

Update:

Preliminary experiments in mice suggest it is possible that the adiponectin receptor AdipoR2 plays a key role in the protective effect of adiponectin in invasive aspergillosis. Our current research could suggest that excessive production of inflammatory cytokines is an important mechanism of pathology in adiponectin-deficient mice. We now have the opportunity to explore a novel pathway that could lead to better treatments for invasive pulmonary aspergillosis, a highly fatal infection with current inadequate treatments that are further threatened by emerging antifungal resistance.

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