title: Neonatal Fc Receptor Regulation of Lung Immunoglobulin and CD103+ Dendritic Cells Confers Transient Susceptibility to Tuberculosis.
abstract: The neonatal Fc receptor (FcRn) extends the systemic half-life of IgG antibodies by chaperoning bound Fc away from lysosomal degradation inside stromal and hematopoietic cells. FcRn also transports IgG across mucosal barriers into the lumen, and yet little is known about how FcRn modulates immunity in the lung during homeostasis or infection. We infected wild-type (WT) and FcRn-deficient (fcgrt(-/-)) mice with Pseudomonas aeruginosa or Mycobacterium tuberculosis to investigate whether recycling and transport of IgG via FcRn influences innate and adaptive immunity in the lung in response to bacterial infection. We found that FcRn expression maintains homeostatic IgG levels in lung and leads to preferential secretion of low-affinity IgG ligands into the lumen. Fcgrt(-/-) animals exhibited no evidence of developmental impairment of innate immunity in the lung and were able to efficiently recruit neutrophils in a model of acute bacterial pneumonia. Although local humoral immunity in lung increased independently of the presence of FcRn during tuberculosis, there was nonetheless a strong impact of FcRn deficiency on local adaptive immunity. We show that the quantity and quality of IgG in airways, as well as the abundance of dendritic cells in the lung, are maintained by FcRn. FcRn ablation transiently enhanced local T cell immunity and neutrophil recruitment during tuberculosis, leading to a lower bacterial burden in lung. This novel understanding of tissue-specific modulation of mucosal IgG isotypes in the lung by FcRn sheds light on the role of mucosal IgG in immune responses in the lung during homeostasis and bacterial disease.
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany vogelzang@mpiib-berlin.mpg.de kaufmann@mpiib-berlin.mpg.de.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vogelzang
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Lozza
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Reece
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Carolina
authors.initials: C
authors.lastname: Perdomo
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zedler
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Hahnke
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Oberbeck-Mueller
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Anca
authors.initials: A
authors.lastname: Dorhoi
authors.affiliation: Max Planck Institute for Infection Biology, Berlin, Germany vogelzang@mpiib-berlin.mpg.de kaufmann@mpiib-berlin.mpg.de.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D058491:Bacterial Load; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004195:Disease Models, Animal; D015395:Histocompatibility Antigens Class I / Q000378:metabolism / Q000502:physiology*; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D039001:Integrin alpha Chains / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000378:metabolism; D009169:Mycobacterium tuberculosis; D022423:Myeloid Cells / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa; D011961:Receptors, Fc / Q000378:metabolism / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D039001:Integrin alpha Chains; D011961:Receptors, Fc; C091367:alpha E integrins; C100688:Fc receptor, neonatal