title: Repeated Mouse Lung Exposures to Stachybotrys chartarum Shift Immune Response from Type 1 to Type 2.
abstract: After a single or multiple intratracheal instillations of Stachybotrys chartarum (S. chartarum or black mold) spores in BALB/c mice, we characterized cytokine production, metabolites, and inflammatory patterns by analyzing mouse bronchoalveolar lavage (BAL), lung tissue, and plasma. We found marked differences in BAL cell counts, especially large increases in lymphocytes and eosinophils in multiple-dosed mice. Formation of eosinophil-rich granulomas and airway goblet cell metaplasia were prevalent in the lungs of multiple-dosed mice but not in single- or saline-dosed groups. We detected changes in the cytokine expression profiles in both the BAL and plasma. Multiple pulmonary exposures to S. chartarum induced significant metabolic changes in the lungs but not in the plasma. These changes suggest a shift from type 1 inflammation after an acute exposure to type 2 inflammation after multiple exposures to S. chartarum. Eotaxin, vascular endothelial growth factor (VEGF), MIP-1α, MIP-1β, TNF-α, and the IL-8 analogs macrophage inflammatory protein-2 (MIP-2) and keratinocyte chemoattractant (KC), had more dramatic changes in multiple- than in single-dosed mice, and parallel the cytokines that characterize humans with histories of mold exposures versus unexposed control subjects. This repeated exposure model allows us to more realistically characterize responses to mold, such as cytokine, metabolic, and cellular changes.
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Jamie H
authors.initials: JH
authors.lastname: Rosenblum Lichtenstein
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Molina
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Donaghey
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|2 Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Yi-Hsiang H
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Mathews
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: David I
authors.initials: DI
authors.lastname: Kasahara
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Park
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: André
authors.initials: A
authors.lastname: Bordini
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: John J
authors.initials: JJ
authors.lastname: Godleski
authors.affiliation: 3 Department of Medicine, University of Illinois College of Medicine, Chicago, Illinois.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Gillis
authors.affiliation: 1 Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Brain
keywords: fungi; inflammation; lymphoid cells; macrophages; metabolome