Neonatal Fc receptor regulation of lung immunoglobulin and CD103+ dendritic cells confers transient susceptibility to tuberculosis

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, yet little is known about how FcRn modulates immunity in the lung during homeostasis or infection. We infected 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 could efficiently recruit neutrophils in a model of acute bacterial pneumonia. Although local humoral immunity in lung increased independently 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 is maintained by FcRn, as well as the abundance of dendritic cells in the lung. FcRn ablation transiently enhanced local T cell immunity and neutrophil recruitment during tuberculosis, leading to 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 for immune responses in the lung during homeostasis and bacterial disease.