title: T-2 toxin impairs murine immune response to respiratory reovirus and exacerbates viral bronchiolitis.
abstract: Exposure to immunosuppressive environmental contaminants is a possible contributing factor to increased occurrence of viral respiratory diseases. The objective of this study was to test the hypothesis that the trichothecene mycotoxin T-2 toxin (T-2), a frequent food contaminant, alters host resistance to lung infection by reovirus, a model respiratory virus. Balb/c mice (4 week old) were treated intraperitoneally with T-2 toxin (1.75 mg/kg bw) or saline vehicle and then intranasally instilled 2 h later with 10(7) plaque forming unit (PFU) of reovirus, strain Lang (T1/L) or saline vehicle. At 10 days post-instillation (PI), both virus plaque-forming responses and reovirus L2 gene expression were 10-fold higher in lungs of T-2-treated mice compared to controls. No-effect and lowest-effect levels for T-2-induced suppression of reovirus clearance were 20 and 200 microg/kg bw, respectively. Respiratory reovirus infection resulted in a mild bronchiolitis with minimal alveolitis, which was markedly exacerbated by T-2 pretreatment. Reovirus exposure induced marked increases in total cells, neutrophils and lymphocytes at 3 and 7 days PI in bronchial alveolar lavage fluid (BALF) whereas macrophages were increased only at 7 days PI. Although prior T-2 exposure attenuated total cell and macrophage counts in BALF of control and infected mice at 3 days PI, the toxin potentiated total cell, macrophage, neutrophil and lymphocyte counts in infected mice at 7 days PI. At 3 days PI, T-2 suppressed reovirus-induced IFN-gamma elevation in BALF, but enhanced production of IL-6 and MCP-1. T-2 pretreatment also suppressed reovirus-specific mucosal IgA responses in lung and enteric tract, but potentiated serum IgA and IgG responses. Taken together, T-2 increased lung viral burden, bronchopneumonia and pulmonary cellular infiltration in reovirus-infected mice. These effects might be attributable to reduced alveolar macrophage levels as well as modulated cytokine and mucosal Ig responses.
authors.affiliation: Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824-1224, USA.
authors.forename: Maoxiang
authors.initials: M
authors.lastname: Li
authors.forename: Jack R
authors.initials: JR
authors.lastname: Harkema
authors.forename: Zahidul
authors.initials: Z
authors.lastname: Islam
authors.forename: Chistopher F
authors.initials: CF
authors.lastname: Cuff
authors.forename: James J
authors.initials: JJ
authors.lastname: Pestka
mesh_terms: D000818:Animals; D001990:Bronchiolitis, Viral / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000821:virology; D018932:Chemokine CCL2 / Q000032:analysis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000032:analysis* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000821:virology; D030102:Orthoreovirus, Mammalian / Q000276:immunology*; D012088:Reoviridae Infections / Q000276:immunology* / Q000473:pathology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000821:virology; D013605:T-2 Toxin / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019562:Viral Load
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D013605:T-2 Toxin