Complement Mediated Signaling on Pulmonary CD103+ Dendritic Cells Is Critical for Their Migratory Function in Response to Influenza Infection

PLoS Pathogens

David M. Kemeny¹  Poon C. Ying²  Baalasubramanian Sivasankar²  Matheswaran Kandasamy²  Hermi R. Sumatoh²  Timothy R. Hughes³  B. Paul Morgan³  Adrian W. S. Ho⁴  Florent Ginhoux⁴  Andreas Schlitzer⁴ 

[1] Immunology Programme and Department of Microbiology, National University of Singapore, Singapore;Infection and Immunity Programme, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore;Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, Wales, United Kingdom;Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore

关键词: Influenza;    T cells;    Cytotoxic T cells;    Complement system;    Complement activation;    Inflammation;    Influenza viruses;    Infectious disease control;   

DOI  :  10.1371/journal.ppat.1003115

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Trafficking of lung dendritic cells (DCs) to the draining lymph node (dLN) is a crucial step for the initiation of T cell responses upon pathogen challenge. However, little is known about the factors that regulate lung DC migration to the dLN. In this study, using a model of influenza infection, we demonstrate that complement component C3 is critically required for efficient emigration of DCs from the lung to the dLN. C3 deficiency affect lung DC-mediated viral antigen transport to the dLN, resulting in severely compromised priming of virus-specific T cell responses. Consequently, C3-deficient mice lack effector T cell response in the lungs that affected viral clearance and survival. We further show that direct signaling by C3a and C5a through C3aR and C5aR respectively expressed on lung DCs is required for their efficient trafficking. However, among lung DCs, only CD103+ DCs make a significant contribution to lung C5a levels and exclusively produce high levels of C3 and C5 during influenza infection. Collectively, our findings show that complement has a profound impact on immune regulation by controlling tissue DC trafficking and highlights a potential utility for complement as an adjuvant in novel vaccine strategies.

【 授权许可】

CC BY