CD11b Regulates Fungal Outgrowth but Not Neutrophil Recruitment in a Mouse Model of Invasive Pulmonary Aspergillosis

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 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 conidia by polymorphonuclear neutrophils (PMN) for control of pulmonary infection. We show that CD11b mice infected with 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 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 conidia than WT PMN . Our study shows that MAC-1 is required for effective clearance of 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.