Mapping the pulmonary environment of animals protected from virulent H1N1 influenza infection using the TLR-2 agonist Pam₂Cys.
We have previously shown that intranasal administration of the Toll-like receptor-2 agonist, S-(2,3-bis(palmitoyloxy)propyl) cysteine (Pam2Cys), provides immediate and antigen independent protection against challenge with influenza virus. Here we characterize the cellular pulmonary environments of mice which had either been treated with Pam2Cys or placebo and then challenged with influenza virus. We show that Pam2Cys treatment results in the influx of innate immune cells into the lungs and that depletion of phagocytic cells from this influx using clodronate-loaded liposomes caused a reduction in the number of interstitial macrophages and monocytes. This resulted in abolition of the protective effect indicating the importance of this cellular subset in Pam2Cys-mediated protection.
Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Edin J
EJ
Mifsud
Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Amabel C L
AC
Tan
Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.|WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Patrick C
PC
Reading
Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
David C
DC
Jackson
D000281:Administration, Intranasal; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004002:Clodronic Acid / Q000008:administration & dosage; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D055666:Lipopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists*
D055666:Lipopeptides; C552442:S-(2,3-bis(palmitoyloxy)propyl)cysteine; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D004002:Clodronic Acid