| First Author | Espinosa V | Year | 2017 |
| Journal | Sci Immunol | Volume | 2 |
| Issue | 16 | PubMed ID | 28986419 |
| Mgi Jnum | J:260886 | Mgi Id | MGI:6140599 |
| Doi | 10.1126/sciimmunol.aan5357 | Citation | Espinosa V, et al. (2017) Type III interferon is a critical regulator of innate antifungal immunity. Sci Immunol 2(16) |
| abstractText | Type III interferons (IFN-lambdas) are the most recently found members of the IFN cytokine family and engage IFNLR1 and IL10R2 receptor subunits to activate innate responses against viruses. We have identified IFN-lambdas as critical instructors of antifungal neutrophil responses. Using Aspergillus fumigatus (Af) as a model to study antifungal immune responses, we found that depletion of CCR2(+) monocytes compromised the ability of neutrophils to control invasive fungal growth. Using an unbiased approach, we identified type I and III IFNs as critical regulators of the interplay between monocytes and neutrophils responding to Af We found that CCR2(+) monocytes are an important early source of type I IFNs that prime optimal expression of IFN-lambda. Type III IFNs act directly on neutrophils to activate their antifungal response, and mice with neutrophil-specific deletion of IFNLR1 succumb to invasive aspergillosis. Dysfunctional neutrophil responses in CCR2-depleted mice were rescued by adoptive transfer of pulmonary CCR2(+) monocytes or by exogenous administration of IFN-alpha and IFN-lambda. Thus, CCR2(+) monocytes promote optimal activation of antifungal neutrophils by initiating a coordinated IFN response. We have identified type III IFNs as critical regulators of neutrophil activation and type I IFNs as early stimulators of IFN-lambda expression. |
