title: Complement mediated signaling on pulmonary CD103(+) dendritic cells is critical for their migratory function in response to influenza infection.
abstract: 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.
authors: Infection and Immunity Programme, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (ASTAR), Singapore.
authors: Matheswaran
authors: M
authors: Kandasamy
authors: Poon C
authors: PC
authors: Ying
authors: Adrian W S
authors: AW
authors: Ho
authors: Hermi R
authors: HR
authors: Sumatoh
authors: Andreas
authors: A
authors: Schlitzer
authors: Timothy R
authors: TR
authors: Hughes
authors: David M
authors: DM
authors: Kemeny
authors: B Paul
authors: BP
authors: Morgan
authors: Florent
authors: F
authors: Ginhoux
authors: Baalasubramanian
authors: B
authors: Sivasankar
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000956:Antigens, Viral; D002465:Cell Movement; D003176:Complement C3 / Q000172:deficiency / Q000378:metabolism*; D015936:Complement C5a / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D039001:Integrin alpha Chains / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000378:metabolism* / Q000401:mortality / Q000821:virology; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate; D013601:T-Lymphocytes / Q000378:metabolism; D019562:Viral Load; D014780:Viruses
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; D003176:Complement C3; D039001:Integrin alpha Chains; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C091367:alpha E integrins; D015936:Complement C5a