Acknowledgements: The authors would like to acknowledge Fraser P. Coxon and Ian Ganley for providing LC3-GFP-mCherry BMDMs. M.S.G. was supported by an FEMS research grant and F.L.v.d.V. was supported by ZonMW under the name EURO-CMC frame of E-Rare-2, the ERA-Net for Research on Rare Diseases.Peer reviewe

Alonso, M Fernanda

Bain, Judith M

Becker, Katharina L

Erwig, Lars P

Gresnigt, Mark S

Leenders, Floris

Meis, Jacques F

van de Veerdonk, Frank L

Wang, Xiaowen

Journal of Innate Immunity

English

Contains fulltext :
                  190697.pdf (publisher's version ) (Open Access

Gresnigt, M.S.

Becker, K.L.

Alonso, M.Fernanda

Meis, J.F.G.M.

Erwig, Lars P.

Veerdonk, F.L. van de

Radboud Repository

Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis

Aberdeen University Research

Invasive aspergillosis mainly occurs in immunocompromised patients and is commonly caused by &lt;i&gt;Aspergillus fumigatus&lt;/i&gt;, while &lt;i&gt;A.&lt;/i&gt;&lt;i&gt;nidulans&lt;/i&gt; is rarely the causative agent. However, in chronic granulomatous disease (CGD) patients, &lt;i&gt;A. nidulans&lt;/i&gt; is a frequent cause of invasive aspergillosis and is associated with higher mortality. Immune recognition of &lt;i&gt;A. nidulans &lt;/i&gt;was compared to &lt;i&gt;A. fumigatus &lt;/i&gt;to offer an insight into why &lt;i&gt;A. nidulans&lt;/i&gt; infections are prevalent in CGD. Live cell imaging with J774A.1 macrophage-like cells and LC3-GFP-mCherry bone marrow-derived macrophages (BMDMs) revealed that phagocytosis of &lt;i&gt;A. nidulans &lt;/i&gt;was slower compared to &lt;i&gt;A. fumigatus&lt;/i&gt;. This difference could be attributed to slower migration of J774A.1 cells and a lower percentage of migrating BMDMs. In addition, delayed phagosome acidification and LC3-associated phagocytosis was observed with &lt;i&gt;A. nidulans&lt;/i&gt;. Cytokine and oxidative burst measurements in human peripheral blood mononuclear cells revealed a lower oxidative burst upon challenge with &lt;i&gt;A. nidulans&lt;/i&gt;. In contrast, &lt;i&gt;A. nidulans&lt;/i&gt; induced significantly higher concentrations of cytokines. Collectively, our data demonstrate that &lt;i&gt;A. nidulans &lt;/i&gt;is phagocytosed and processed at a slower rate compared to &lt;i&gt;A. fumigatus,&lt;/i&gt; resulting in reduced fungal killing and increased germination of conidia. This slower rate of &lt;i&gt;A. nidulans&lt;/i&gt; clearance may be permissive for overgrowth within certain immune settings.</jats:p

Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis

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