title: MyD88 controls human metapneumovirus-induced pulmonary immune responses and disease pathogenesis.
abstract: Human metapneumovirus (hMPV) is a common cause of lung and airway infections in infants and young children. Recently, we and others have shown that hMPV infection induces Toll-like receptor (TLR)-dependent cellular signaling. However, the contribution of TLR-mediated signaling in host defenses against pulmonary hMPV infection and associated disease pathogenesis has not been elucidated. In this study, mice deficient in MyD88, a common adaptor of TLRs, was used to investigate the contribution of TLRs to in vivo pulmonary response to hMPV infection. MyD88(-/-) mice have significantly reduced pulmonary inflammation and associated disease compared with wild-type (WT) C57BL/6 mice after intranasal infection with hMPV. hMPV-induced cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and isolated lung conventional dendritic cells (cDC) are also significantly impaired by MyD88 deletion. In addition, we found that MyD88 is required for the recruitment of DC, T cells, and other immune cells to the lungs, and for the functional regulation of DC and T cells in response to hMPV infection. Taken together, our data indicate that MyD88-mediated pathways are essential for the pulmonary immune and pathogenic responses to this viral pathogen.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, United States.
authors.forename: Junping
authors.initials: J
authors.lastname: Ren
authors.forename: Deepthi
authors.initials: D
authors.lastname: Kolli
authors.forename: Junfang
authors.initials: J
authors.lastname: Deng
authors.forename: Rong
authors.initials: R
authors.lastname: Fang
authors.forename: Bin
authors.initials: B
authors.lastname: Gong
authors.forename: Megan
authors.initials: M
authors.lastname: Xue
authors.forename: Antonella
authors.initials: A
authors.lastname: Casola
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Garofalo
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Garafalo
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Bao
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002465:Cell Movement; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000821:virology; D029121:Metapneumovirus / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000378:metabolism*; D018184:Paramyxoviridae Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology
chemical_list: D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88
keywords: Cytokines/chemokines; MyD88; Pulmonary immune response; hMPV