title: Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection.
abstract: Aspergillus fumigatus, a ubiquitous fungus, causes invasive disease in immunocompromised humans. Although monocytes and antigen-specific CD4 T cells contribute to defense against inhaled fungal spores, how these cells interact during infection remains undefined. Investigating the role of inflammatory monocytes and monocyte-derived dendritic cells during fungal infection, we find that A. fumigatus infection induces an influx of chemokine receptor CCR2- and Ly6C-expressing inflammatory monocytes into lungs and draining lymph nodes. Depletion of CCR2(+) cells reduced A. fumigatus conidial transport from lungs to draining lymph nodes, abolished CD4 T cell priming following respiratory challenge, and impaired pulmonary fungal clearance. In contrast, depletion of CCR2(+)Ly6C(hi) monocytes during systemic fungal infection did not prevent CD4 T cell priming in the spleen. Our findings demonstrate that pulmonary CD4 T cell responses to inhaled spores require CCR2(+)Ly6C(hi) monocytes and their derivatives, revealing a compartmentally restricted function for these cells in adaptive respiratory immune responses.
authors.affiliation: Infectious Disease Service, Department of Medicine, and Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. thohl@fhcrc.org
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Hohl
authors.forename: Amariliz
authors.initials: A
authors.lastname: Rivera
authors.forename: Lauren
authors.initials: L
authors.lastname: Lipuma
authors.forename: Alena
authors.initials: A
authors.lastname: Gallegos
authors.forename: Chao
authors.initials: C
authors.lastname: Shi
authors.forename: Mathias
authors.initials: M
authors.lastname: Mack
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000950:Antigens, Ly / Q000276:immunology* / Q000378:metabolism; D001232:Aspergillus fumigatus; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D055732:Pulmonary Aspergillosis / Q000276:immunology*; D054390:Receptors, CCR2 / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology
chemical_list: D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; D054390:Receptors, CCR2