title: Mycobacterium tuberculosisCell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection.
abstract: In 2016, the World Health Organization reported that one person dies of tuberculosis (TB) every 21 s. A host environment thatMycobacterium tuberculosis(M.tb) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. We published that human lung mucosa, or alveolar lining fluid (ALF), contains an array of hydrolytic enzymes that can significantly alter theM.tbsurface during infection by cleaving off parts of its cell wall. This interaction results in two different outcomes: modifications on theM.tbcell wall surface and release ofM.tbcell wall fragments into the environment. Typically, one of the first host immune cells at the site ofM.tbinfection is the neutrophil. Neutrophils can mount an extracellular and intracellular innate immune response toM.tbduring infection. We hypothesized that exposure of neutrophils to ALF-inducedM.tbreleased cell wall fragments would prime neutrophils to controlM.tbinfection better. Our results show that ALF fragments activate neutrophils leading to an increased production of inflammatory cytokines and oxidative radicals. However, neutrophil exposure to these fragments reduces production of chemoattractants (i.e., interleukin-8), and degranulation, with the subsequent reduction of myeloperoxidase release, and does not induce cytotoxicity. Unexpectedly, these ALF fragment-derived modulations in neutrophil activity do not further, either positively or negatively, contribute to the intracellular control ofM.tbgrowth during infection. However, secreted products from neutrophils primed with ALF fragments are capable of regulating the activity of resting macrophages. These results indicate that ALF-inducedM.tbfragments could further contribute to the control ofM.tbgrowth and local killing by resident neutrophils by switching on the total oxidative response and limiting migration of neutrophils to the infection site.
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Scordo
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Jesús
authors.initials: J
authors.lastname: Arcos
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Holden V
authors.initials: HV
authors.lastname: Kelley
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Diangelo
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Smitha J
authors.initials: SJ
authors.lastname: Sasindran
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Ellie
authors.initials: E
authors.lastname: Youngmin
authors.affiliation: Department of Internal Medicine, Pulmonary, Critical Care & Sleep Medicine Division, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wewers
authors.affiliation: Department of Internal Medicine, Infectious Disease Division, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Pathology, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Joan-Miquel
authors.initials: JM
authors.lastname: Balada-Llasat
authors.affiliation: Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, College of Medicine, The Ohio State University , Columbus, OH , USA.
authors.forename: Jordi B
authors.initials: JB
authors.lastname: Torrelles
keywords: cell wall; innate immunity; lung mucosa; neutrophil; tuberculosis