Vaccine and Infectious Disease Division

Dissecting the immune response to an infectious fungus

Most of us inhale ubiquitous fungal spores every day, but for those with healthy immune systems, these events usually pass unnoticed.  The opportunistic fungus Aspergillus fumigatus can cause life-threatening disease in immunocompromised people, but is cleared rapidly by pulmonary immune cells in healthy persons.  To address which immune cells are involved in this process and how they interact to generate protective responses, VIDI assistant member Dr. Tobias Hohl and colleagues created a novel mouse strain in which they could deplete at-will a certain type of immune cell, the inflammatory monocyte.

By comparing the outcome of Aspergillus infection in normal mice and in mice depleted of inflammatory monocytes, the researchers found that these cells are invaluable in helping direct the correct kind of T cell response to the lungs, where the fungal spores attempt to germinate.  Specifically, they found that inflammatory monocytes traffic rapidly to the lungs and lymph nodes after fungal infection in healthy mice.  Normally, the immune system transports the fungal spores from the lungs to the draining lymph node to prime protective fungus-specific T cell responses.  Hohl and colleagues found that when they depleted inflammatory monocytes, fungal spores remained in the lungs, indicating that inflammatory monocytes are essential for this transport step.  This defect in fungal spore transport severely dampened protective T cell responses in the lung.

 The requirement for inflammatory monocytes in facilitating microbe-specific T cell responses was further determined to be tissue-specific – essential for lung T cell responses, but dispensable for spleen T cell responses. These results suggest that monocytes may play an important role in the induction of antifungal adaptive immune responses in the human lung and that monocyte deficiency or dysfunction in high-risk patient groups contributes to the risk of developing invasive aspergillosis. 

Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection.  Hohl TM, Rivera A, Lipuma L, Gallegos A, Shi C, Mack M, Pamer EG.  Cell Host Microbe. 2009 Nov 19;6(5):470-81.