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However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection by\n            <jats:italic>Mucor circinelloides<\/jats:italic>\n            spores are modeled by a combined\n            <jats:italic>in silico<\/jats:italic>\n            modeling approach and real-time\n            <jats:italic>in vivo<\/jats:italic>\n            microscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onset\n            <jats:italic>in vivo<\/jats:italic>\n            .\n            <jats:italic>In silico<\/jats:italic>\n            analysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment and the importance of inhibition of spore germination for protection from active fungal disease. These\n            <jats:italic>in silico<\/jats:italic>\n            data are supported by an\n            <jats:italic>in vivo<\/jats:italic>\n            lack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomas\n            <jats:italic>in vivo<\/jats:italic>\n            . Disease can be reactivated by immunosuppression. Together, these data represent the first\n            <jats:italic>in vivo<\/jats:italic>\n            real-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Mucormycosis is a dramatic fungal infection frequently leading to the death of patients. We know little about the immune response to the fungus causing this infection, although evidence points toward defects in early immune events after infection. Here, we dissect this early immune response to infectious fungal spores. We show that specialized white blood cells (phagocytes) rapidly respond to these spores and accumulate around the fungus. However, we demonstrate that the mechanisms that enable phagocytes to kill the fungus fail, allowing for survival of spores. Instead a cluster of phagocytes resembling an early granuloma is formed around spores to control the latent infection. This study is the first detailed analysis of early granuloma formation during a fungal infection highlighting a latent stage that needs to be considered for clinical management of patients.\n          <\/jats:p>","DOI":"10.1128\/mbio.02010-17","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T09:46:36Z","timestamp":1522057596000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Robust Phagocyte Recruitment Controls the Opportunistic Fungal Pathogen\n            <i>Mucor circinelloides<\/i>\n            in Innate Granulomas\n            <i>In Vivo<\/i>"],"prefix":"10.1128","volume":"9","author":[{"given":"Sarah","family":"Inglesfield","sequence":"first","affiliation":[{"name":"Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom"},{"name":"School of Mathematics, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Jasiulewicz","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom"},{"name":"School of Biosciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Hopwood","sequence":"additional","affiliation":[{"name":"School of Mathematics, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Tyrrell","sequence":"additional","affiliation":[{"name":"School of Mathematics, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Youlden","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom"},{"name":"School of Mathematics, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mazon-Moya","sequence":"additional","affiliation":[{"name":"Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owain R.","family":"Millington","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy &amp; Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7286-6503","authenticated-orcid":false,"given":"Serge","family":"Mostowy","sequence":"additional","affiliation":[{"name":"Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Jabbari","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom"},{"name":"School of Mathematics, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Voelz","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom"},{"name":"School of Biosciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir865"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.5858\/2001-125-0375-HFOZ"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.3.556-569.2005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/00362177685190041"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir866"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004404"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2007.140087"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780802326001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-006-0107-1"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.2.236-301.2000"},{"key":"e_1_3_2_12_2","first-page":"243","article-title":"Pulmonary defense mechanisms against opportunistic fungal pathogens","volume":"47","author":"Waldorf AR","year":"1989","unstructured":"Waldorf AR. 1989. 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