Human MAITcells are rapidly activated by Aspergillus spp. in an APC-dependent manner.

Abstract

Mucosal associated invariant Tcells (MAITcells) are innate-like Tcells (TC) which are known to be activated by several bacteria and viruses. However, activation of MAITcells by moulds, such as the opportunistic human pathogen Aspergillus, is not well described. Stimulation of human PBMC with A. fumigatus, A. flavus, or A. terreus conidia revealed that in contrast to conventional CD4+ and CD8+ TC, MAITcells responded already after 4 h of coincubation with upregulation of CD69. Furthermore, concurrent increase of CD107a expression and reduced intracellular expression of cytolytic proteins like perforin and granzyme indicated degranulation of intracellular vesicles. MAITcell activation only occurred in the presence of APC and was dependent on cell-cell contact as separation of TC and APC abrogated MAITcell activation. Furthermore, we observed that MAITcell activation by moulds requires presentation of riboflavin metabolites and depends on TCR engagement as antibody blocking of MR1, the antigen presenting molecule for MAITcells, prevented upregulation of CD69 and CD107a. In summary, we could demonstrate that MAITcells are activated by Aspergillus conidia in a TCR-dependent manner by APC. These findings reveal MAITcells as an interesting new target in antifungal defense.