title: Role of TLR4 in allergic sensitization to food proteins in mice.
abstract: Allergic sensitization to food proteins and other allergens is increasing in prevalence. One hypothesis for this increase is that the decreased rate of infections or exposure to microbial products leaves the immune system susceptible to inappropriate reactivity to innocuous antigens through the lack of development of regulatory cells. We hypothesized that constitutive Toll-like receptor (TLR)4 signaling (presumably via the commensal flora) could inhibit the development of allergic sensitization to food proteins. We tested this hypothesis by sensitizing TLR4+ and TLR4- mice on two genetic backgrounds, C3H and BALB/c, to two common food allergens [beta-lactoglobulin (betaLG) and peanut (PN)]. B-cell responses were not significantly influenced by TLR4 status. T-cell responses were Th2 skewed in TLR4-deficient C3H mice compared with TLR4 sufficient C3H mice, but this pattern of Th2 skewing was not observed in TLR4-deficient mice on a BALB/c background. In anaphylaxis-susceptible C3H mice, TLR4 deficiency was associated with increased severity of anaphylaxis to PN, and decreased severity of anaphylaxis to betaLG. In anaphylaxis-resistant BALB/c mice, TLR4 deficiency was not sufficient to render mice susceptible to PN-induced anaphylaxis. We conclude that although TLR4 status can influence T-cell responses and anaphylaxis severity, the nature of the influence is highly antigen- and strain-dependent.
authors.affiliation: Division of Pediatric Allergy and Immunology and the Jaffe Institute for Food Allergy, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Berin
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.forename: M
authors.initials: M
authors.lastname: Domaradzki
authors.forename: X-M
authors.initials: XM
authors.lastname: Li
authors.forename: H A
authors.initials: HA
authors.lastname: Sampson
mesh_terms: D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology* / Q000503:physiopathology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005512:Food Hypersensitivity / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011336:Probability; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000502:physiology
chemical_list: D000485:Allergens; D016207:Cytokines; D051197:Toll-Like Receptor 4