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Understanding how calcineurin inhibitors impair fungal immunity is a key priority for defining risk of infection. Here, we show that the calcineurin inhibitor tacrolimus\u00a0impairs clearance of the major mould pathogen\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    from the airway, by inhibiting macrophage inflammatory responses. This leads to defective early neutrophil recruitment and fungal clearance. We confirm these findings in zebrafish, showing an evolutionarily conserved role for calcineurin signalling in neutrophil recruitment during inflammation. We find that calcineurin\u2013NFAT activation is phagocytosis dependent and collaborates with NF\u2010\u03baB for TNF\u2010\u03b1 production. For yeast zymosan particles, activation of macrophage calcineurin\u2013NFAT occurs via the phagocytic Dectin\u20101\u2013spleen tyrosine kinase pathway, but for\n                    <jats:italic>A.\u00a0fumigatus<\/jats:italic>\n                    , activation occurs via a phagosomal TLR9\u2010dependent and Bruton's tyrosine kinase\u2010dependent signalling pathway that is independent of MyD88. We confirm the collaboration between NFAT and NF\u2010\u03baB for TNF\u2010\u03b1 production in primary alveolar macrophages. These observations identify inhibition of a newly discovered macrophage TLR9\u2013BTK\u2013calcineurin\u2013NFAT signalling pathway as a key immune defect that leads to organ transplant\u2010related invasive aspergillosis.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201404556","type":"journal-article","created":{"date-parts":[[2015,1,31]],"date-time":"2015-01-31T02:51:59Z","timestamp":1422672719000},"page":"240-258","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":177,"title":["Phagocytosis\u2010dependent activation of a TLR9\u2013BTK\u2013calcineurin\u2013NFAT pathway co\u2010ordinates innate immunity to Aspergillus fumigatus"],"prefix":"10.1038","volume":"7","author":[{"given":"Susanne","family":"Herbst","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mazon Moya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Marzola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Birrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinobu","family":"Saijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Mostowy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Shaunak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius","family":"Armstrong\u2010James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,1,30]]},"reference":[{"key":"BFEMMM201404556_CR1","doi-asserted-by":"crossref","first-page":"12957","DOI":"10.1523\/JNEUROSCI.1064-09.2009","volume":"29","author":"HM Abdul","year":"2009","unstructured":"Abdul HM, Sama MA, Furman JL, Mathis DM, Beckett TL, Weidner AM, Patel ES, Baig I, Murphy MP, LeVine H III et\u00a0al (2009) Cognitive decline in Alzheimer's disease is associated with selective changes in calcineurin\/NFAT signaling. 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