Dr. Maziar Divangahi and his postdoctoral fellow Dr. Erwan Pernet are on a promising path towards developing flu treatment using a lipid target. They identified a new role for the lipid mediator Leukotriene B4 in the lung. In a study published in Nature Microbiology, they show that the LTB4 molecule is capable of not only reducing collateral tissue damage caused by immune responses but also enhancing host survival.
“The influenza virus is not the only threat; the host’s own immune response is mainly responsible for jeopardizing host survival. Therefore, it is essential to understand the regulatory mechanisms that maintain the tight balance between protective and harmful immunity.”– Erwan Pernet
Influenza remains a global public health challenge, according to the World Health Organization. Each year, there are an estimated one billion people cases worldwide, resulting in 290,000 to 650,000 influenza-related respiratory deaths.
Dr. Divangahi’s laboratory has focused on new immunotherapies targeting the immune system via host lipid mediators to either effectively kill the virus or limit lung tissue damage. In this study, they focused on the LTB4 lipid mediator and its effects on the immune response to flu infection. After working with mice lacking the receptor for LTB4, they were able to identify a network of regulatory mechanisms that maintain the tight balance between protective and harmful immunity. Also, of particular importance to future clinical studies was the finding that a single dose of LTB4 at the peak of disease was enough to significantly reduce lung immunopathology and tissue damage and improve host survival.
“For the first time we show there is a subtype of macrophages in the lungs that are able to produce this immunoregulatory lipid (LTB4) to reduce the inflammation caused by another macrophage population that is responsible for causing lung tissue damage during influenza infection.”– Maziar Divangahi
View the full publication here:
Leukotriene B4-type I interferon axis regulates macrophage-mediated disease tolerance to influenza infection. Pernet E, Downey J, Vinh DC, Powell WS, Divangahi M. Nat Microbiol. 2019 May 20. doi: 10.1038/s41564-019-0444-3. PMID: 31110361
The research was also featured in the CIHR-III (institute of Infection and Immunity) newsletter!