title: Lanthionine Synthetase C-Like 2 Modulates Immune Responses to Influenza Virus Infection.
abstract: Broad-based, host-targeted therapeutics have the potential to ameliorate viral infections without inducing antiviral resistance. We identified lanthionine synthetase C-like 2 (LANCL2) as a new therapeutic target for immunoinflammatory diseases. To examine the therapeutic efficacy of oral NSC61610 administration on influenza, we infected C57BL/6 mice with influenza A H1N1pdm virus and evaluated influenza-related mortality, lung inflammatory profiles, and pulmonary histopathology. Oral treatment with NSC61610 ameliorates influenza virus infection by down-modulating pulmonary inflammation through the downregulation of TNF-α and MCP-1 and reduction in the infiltration of neutrophils. NSC61610 treatment increases IL10-producing CD8+ T cells and macrophages in the lungs during the resolution phase of disease. The loss of LANCL2 or neutralization of IL-10 in mice infected with influenza virus abrogates the ability of NSC61610 to accelerate recovery and induce IL-10-mediated regulatory responses. These studies validate that oral treatment with NSC61610 ameliorates morbidity and mortality and accelerates recovery during influenza virus infection through a mechanism mediated by activation of LANCL2 and subsequent induction of IL-10 responses by CD8+ T cells and macrophages in the lungs.
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute, Virginia Tech , Blacksburg, VA , USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Leber
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute, Virginia Tech , Blacksburg, VA , USA.
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute, Virginia Tech , Blacksburg, VA , USA.
authors.forename: Nuria
authors.initials: N
authors.lastname: Tubau-Juni
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute, Virginia Tech , Blacksburg, VA , USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Zoccoli-Rodriguez
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute, Virginia Tech , Blacksburg, VA , USA.
authors.forename: Pinyi
authors.initials: P
authors.lastname: Lu
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute, Virginia Tech , Blacksburg, VA , USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Godfrey
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute, Virginia Tech , Blacksburg, VA , USA.
authors.forename: Shiv
authors.initials: S
authors.lastname: Kale
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute, Virginia Tech , Blacksburg, VA , USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
keywords: IL-10; LANCL2; drug discovery; immunoregulation; infection resolution; influenza virus