An unusual Toll/MyD88-mediated <i>Drosophila</i> host defence against <i>Talaromyces marneffei</i>

Talaromycosis, caused by <i>Talaromyces marneffei</i> (<i>T. marneffei</i>, formerly known as <i>Penicillium marneffei</i>), is an opportunistic invasive mycosis endemic in tropical and subtropical areas of Asia with high mortality rate. Despite various infection models established to study the immunological interaction between <i>T. marneffei</i> and the host, the pathogenicity of this fungus is not yet fully understood. So far, <i>Drosophila melanogaster</i>, a well-established genetic model organism to study innate immunity, has not been used in related research on <i>T. marneffei</i>. In this study, we provide the initial characterization of a systemic infection model of <i>T. marneffei</i> in the <i>D. melanogaster</i> host. Survival curves and fungal loads were tested as well as Toll pathway activation was quantified by RT-qPCR of several antimicrobial peptide (AMP) genes including <i>Drosomycin</i>, <i>Metchnikowin</i>, and <i>Bomanin Short 1</i>. We discovered that whereas most wild-type flies were able to overcome the infection, <i>MyD88</i> or <i>Toll</i> mutant flies failed to prevent fungal dissemination and proliferation and ultimately succumbed to this challenge. Unexpectedly, the induction of classical Toll pathway activation readouts, <i>Drosomycin</i> and <i>Bomanin Short 1</i>, by live or killed <i>T. marneffei</i> was quite limited in wild-type flies, suggesting that the fungus largely escapes detection by the systemic immune system. This unusual situation of a poor systemic activation of the Toll pathway and a strong susceptibility phenotype of <i>MyD88</i>/<i>Toll</i> might be accounted for by a requirement for this host defence in only specific tissues, a hypothesis that remains to be rigorously tested.