In:
The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 67.29-67.29
Abstract:
Type I (IFN-α/β) and Type III (IFN-λ) interferons are important mediators of antiviral immunity but whether they are required for antifungal defense is unclear. We report that mice defective in Type I and/or Type III IFN receptor expression are highly susceptible to infection with the opportunistic human fungal pathogen Aspergillus fumigatus (Af). Type I IFN (IFNAR) and Type III (IFNLR1) receptor expression on hematopoietic cells was required for antifungal defense while their expression on non-hematopoietic was dispensable. Consistently, mice with gene-specific deletion of IFNLR1 or STAT-1 on granulocytes were highly susceptible to Af. These data demonstrate a requisite and non-redundant role for Type I and Type III IFNs for the activation of antifungal immunity. In addition, we found that Type III IFNs act as important activators of reactive oxygen species generation in antifungal neutrophils, and require early expression of Type I IFN for optimal induction. Importantly, CCR2+ monocytes act as an important source of Type I IFN, and are required for the optimal expression of Type III IFN and fully functional neutrophil antifungal activity. Dysfunctional neutrophil responses in CCR2-depleted mice were rescued by adoptive transfer of pulmonary CCR2+ monocytes or by exogenous administration of IFN-a and IFN-l. Altogether, our data identified Type III IFNs as major regulators of neutrophil activation, and Type I IFNs as early activators of IFN-λ expression and response. Innate antifungal defense is thus coordinated by the actions of Type I and Type III IFNs, a finding that suggests a broader therapeutic potential for these cytokines as activators of antifungal immunity.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.204.Supp.67.29
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2020
detail.hit.zdb_id:
1475085-5
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