AUTHOR=Teschner Daniel , Cholaszczyńska Anna , Ries Frederic , Beckert Hendrik , Theobald Matthias , Grabbe Stephan , Radsak Markus , Bros Matthias TITLE=CD11b Regulates Fungal Outgrowth but Not Neutrophil Recruitment in a Mouse Model of Invasive Pulmonary Aspergillosis JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00123 DOI=10.3389/fimmu.2019.00123 ISSN=1664-3224 ABSTRACT=

ß2 integrin receptors consist of an alpha subunit (CD11a-CD11d) and CD18 as the common beta subunit, and are differentially expressed by leukocytes. ß2 integrins are required for cell-cell interaction, transendothelial migration, uptake of opsonized pathogens, and cell signaling processes. Functional loss of CD18—termed leukocyte-adhesion deficiency type 1 (LAD1)—results in an immunocompromised state characterized by frequent occurrence of severe infections. In immunosuppressed individuals Aspergillus fumigatus is a frequent cause of invasive pulmonary fungal infection, and often occurs in patients suffering from LAD1. Here, we asked for the importance of CD11b/CD18 also termed MAC-1 which is required for phagocytosis of opsonized A. fumigatus conidia by polymorphonuclear neutrophils (PMN) for control of pulmonary A. fumigatus infection. We show that CD11b−/− mice infected with A. fumigatus were unaffected in long term survival, similar to wild type (WT) mice. However, bronchoalveolar lavage (BAL) performed 1 day after infection revealed a higher lung infiltration of PMN in case of infected CD11b−/− mice than observed for WT mice. BAL derived from infected CD11b−/− mice also contained a higher amount of leukocyte-attracting CCL5 chemokine, but lower amounts of proinflammatory innate cytokines. In accordance, lung tissue of A. fumigatus infected CD11b−/− mice was characterized by lower cellular inflammation, and a higher fungal burden. In agreement, CD11b−/−PMN exerted lower phagocytic activity on serum-opsonized A. fumigatus conidia than WT PMN in vitro. Our study shows that MAC-1 is required for effective clearance of A. fumigatus by infiltrating PMN, and the establishment of an inflammatory microenvironment in infected lung. Enhanced infiltration of CD11b−/− PMN may serve to compensate impaired PMN function.