Shaping the lung IL-22 response during invasive aspergillosis (INC4P.325)

Abstract

Exposure to the opportunistic mold Aspergillus fumigatus may result in a wide range of infectious diseases. Among these infections, invasive aspergillosis is the most common and the most lethal. Our lab has previously shown a protective role for Dectin-dependent IL-22 production. In our current studies we sought to identify potential cell source(s) of IL-22 as well as factors critical for its production during invasive aspergillosis. Employing human CD4 IL-22 reporter mice, we show that iNKT cells and γδ T cells are sources of IL-22 48 h post-A. fumigatus exposure. In subsequent studies, we observed an early impairment in IL-22 production by lung cells from CD1d deficient (iNKT deficient) mice that returned to wild type levels by 48 h. In contrast, mice deficient in γδ T cells had relatively intact IL-22 production early after A. fumigatus exposure that became significantly attenuated by 48 h post-challenge. In order to identify factors critical for IL-22 production we interrogated the role of several pertinent transcription factors including: related orphan receptor-γ (RORγ), the aryl hydrocarbon receptor (Ahr), MyD88, and TRIF. Collectively, our data shows that iNKT cells and γδ T cells support early vs. late IL-22 production, which is fully dependent on RORγ and MyD88, partially dependent on Ahr, and independent of TRIF.