title: Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression.
abstract: Elevated levels of combustion-derived particulate matter (CDPM) are a risk factor for the development of lung diseases such as asthma. Studies have shown that CDPM exacerbates asthma, inducing acute lung dysfunction and inflammation; however, the impact of CDPM exposure on early immunological responses to allergens remains unclear. To determine the effects of early-life CDPM exposure on allergic asthma development in infants, we exposed infant mice to CDPM and then induced a mouse model of asthma using house dust mite (HDM) allergen. Mice exposed to CDPM+HDM failed to develop a typical asthma phenotype including airway hyper-responsiveness, T-helper type 2 (Th2) inflammation, Muc5ac expression, eosinophilia, and HDM-specific immunoglobulin (Ig) compared with HDM-exposed mice. Although HDM-specific IgE was attenuated, total IgE was twofold higher in CDPM+HDM mice compared with HDM mice. We further demonstrate that CDPM exposure during early life induced an immunosuppressive environment in the lung, concurrent with increases in tolerogenic dendritic cells and regulatory T cells, resulting in the suppression of Th2 responses. Despite having early immunosuppression, these mice develop severe allergic inflammation when challenged with allergen as adults. These findings demonstrate a mechanism whereby CDPM exposure modulates adaptive immunity, inducing specific antigen tolerance while amplifying total IgE, and leading to a predisposition to develop asthma upon rechallenge later in life.
authors.affiliation: 1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, USA [2] Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
authors.forename: J
authors.initials: J
authors.lastname: Saravia
authors.affiliation: 1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, USA [2] Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
authors.forename: D
authors.initials: D
authors.lastname: You
authors.affiliation: Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: P
authors.initials: P
authors.lastname: Thevenot
authors.affiliation: 1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, USA [2] Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
authors.forename: G I
authors.initials: GI
authors.lastname: Lee
authors.affiliation: 1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, USA [2] Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
authors.forename: B
authors.initials: B
authors.lastname: Shrestha
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lomnicki
authors.affiliation: 1] Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, USA [2] Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Cormier
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004781:Environmental Exposure / Q000009:adverse effects*; D007165:Immunosuppression Therapy; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009093:Mucus / Q000378:metabolism; D052638:Particulate Matter / Q000009:adverse effects*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D000941:Antigens; D052638:Particulate Matter