Giuseppe
Emeritus
Prophylactic Administration of Bacterially Derived Immunomodulators Improves the Outcome of Influenza Infection in a Murine Model. (J Virol., abstract, edited, RA-1005)
J Virol. 2010 Jan 6. [Epub ahead of print]
Prophylactic Administration of Bacterially Derived Immunomodulators Improves the Outcome of Influenza Infection in a Murine Model.
Norton EB, Clements JD, Voss TG, C?rdenas-Freytag L. - Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112.
Prophylactic or therapeutic immunomodulation is an antigen-independent strategy, which induces nonspecific immune system activation, thereby enhancing host defense to disease. In this study, we investigated the effect of prophylactic immunomodulation on the outcome of influenza infection using three bacterially derived immune enhancing agents known for promoting distinct immunological profiles. Balb/c mice were treated per nasally with either cholera toxin (CT), a mutant form of the CT-related E. coli heat-labile enterotoxin, designated LT(R192G), or CpG ODN. Mice were subsequently challenged with a lethal dose of Influenza A/PR/8/34 virus 24 hrs after the last immunomodulation treatment and either monitored for survival or sacrificed post-challenge for viral and immunological analysis. Treatment with the three immunomodulators prevented or delayed mortality and weight loss, but only CT or LT(R192G) significantly reduced initial lung viral loads measured by plaque assay. Analysis performed four days post-infection indicated that prophylactic treatments with CT, LT(R192G), or CpG resulted in significantly increased numbers of CD4 T-cells, B-cells, and dendritic cells, and altered costimulatory marker expression in the airways of infected mice, coinciding with reduced expression of pulmonary chemokines and the appearance of iBALT-like structures in the lungs. Collectively, these results suggest that, despite different immunomodulatory mechanisms, CT, LT(R192G) and CpG induce an initial inflammatory process and enhance the immune response to primary influenza challenge while preventing potentially damaging chemokine expression. These studies provide insight into the immunological parameters and immune modulation strategies that have the potential to enhance the non-specific host response to influenza infection.
PMID: 20053748 [PubMed - as supplied by publisher]
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J Virol. 2010 Jan 6. [Epub ahead of print]
Prophylactic Administration of Bacterially Derived Immunomodulators Improves the Outcome of Influenza Infection in a Murine Model.
Norton EB, Clements JD, Voss TG, C?rdenas-Freytag L. - Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, 70112.
Prophylactic or therapeutic immunomodulation is an antigen-independent strategy, which induces nonspecific immune system activation, thereby enhancing host defense to disease. In this study, we investigated the effect of prophylactic immunomodulation on the outcome of influenza infection using three bacterially derived immune enhancing agents known for promoting distinct immunological profiles. Balb/c mice were treated per nasally with either cholera toxin (CT), a mutant form of the CT-related E. coli heat-labile enterotoxin, designated LT(R192G), or CpG ODN. Mice were subsequently challenged with a lethal dose of Influenza A/PR/8/34 virus 24 hrs after the last immunomodulation treatment and either monitored for survival or sacrificed post-challenge for viral and immunological analysis. Treatment with the three immunomodulators prevented or delayed mortality and weight loss, but only CT or LT(R192G) significantly reduced initial lung viral loads measured by plaque assay. Analysis performed four days post-infection indicated that prophylactic treatments with CT, LT(R192G), or CpG resulted in significantly increased numbers of CD4 T-cells, B-cells, and dendritic cells, and altered costimulatory marker expression in the airways of infected mice, coinciding with reduced expression of pulmonary chemokines and the appearance of iBALT-like structures in the lungs. Collectively, these results suggest that, despite different immunomodulatory mechanisms, CT, LT(R192G) and CpG induce an initial inflammatory process and enhance the immune response to primary influenza challenge while preventing potentially damaging chemokine expression. These studies provide insight into the immunological parameters and immune modulation strategies that have the potential to enhance the non-specific host response to influenza infection.
PMID: 20053748 [PubMed - as supplied by publisher]
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