title: APRIL affects antibody responses and early leukocyte infiltration, but not influenza A viral control.
abstract: A proliferation inducing ligand (APRIL) is implicated in the regulation of class switch recombination to IgA in T-independent B cell responses. Since B cells play an important role in the immunity to influenza A virus and resistance against the virus is partly controlled by T-independent IgA B cell responses, we studied the role of APRIL during an influenza A infection in vivo. APRIL transgenic, wild-type and APRIL deficient mice were intranasally infected with a non-lethal dose of a mouse adapted strain of influenza A. Compared to wild-type mice, APRIL deficient mice showed a twofold reduction in the amount of macrophages in the lungs and a tendency towards decreased granulocyte influx in the early leukocyte recruitment phase. Although the T cell immune response against influenza was unaffected, APRIL Tg mice showed prolonged influenza-specific IgM production and differential class switching. Unexpectedly, the IgA B cell response was completely T helper cell dependent and also not affected by the absence or presence of APRIL. In addition, viral clearance and recovery from the infection was not influenced by APRIL. Combined these results indicate that APRIL affects specific aspects of the anti-influenza response, but plays a limited role in disease recovery.
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Gijs
authors.initials: G
authors.lastname: Hardenberg
authors.forename: Koen
authors.initials: K
authors.lastname: van der Sluijs
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001835:Body Weight; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002452:Cell Count; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D037181:Lectins, C-Type; D007962:Leukocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation; D019562:Viral Load; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018932:Chemokine CCL2; D015850:Interleukin-6; D037181:Lectins, C-Type; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D000099192:CD69 Antigens; C491768:Ccl2 protein, mouse; C491959:Tnfsf13 protein, mouse