title: L-plastin is essential for alveolar macrophage production and control of pulmonary pneumococcal infection.
abstract: We report that mice deficient for the hematopoietic-specific, actin-bundling protein L-plastin (LPL) succumb rapidly to intratracheal pneumococcal infection. The increased susceptibility of LPL(-/-) mice to pulmonary pneumococcal challenge correlated with reduced numbers of alveolar macrophages, consistent with a critical role for this cell type in the immediate response to pneumococcal infection. LPL(-/-) mice demonstrated a very early clearance defect, with an almost 10-fold-higher bacterial burden in the bronchoalveolar lavage fluid 3 h following infection. Clearance of pneumococci from the alveolar space in LPL(-/-) mice was defective compared to that in Rag1(-/-) mice, which lack all B and T lymphocytes, indicating that innate immunity is defective in LPL(-/-) mice. We did not identify defects in neutrophil or monocyte recruitment or in the production of inflammatory cytokines or chemokines that would explain the early clearance defect. However, efficient alveolar macrophage regeneration following irradiation required LPL. We thus identify LPL as being key to alveolar macrophage development and essential to an effective antipneumococcal response. Further analysis of LPL(-/-) mice will illuminate critical regulators of the generation of alveolar macrophages and, thus, effective pulmonary innate immunity.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, Saint Louis, Missouri, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Deady
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Todd
authors.forename: Chris G
authors.initials: CG
authors.lastname: Davis
authors.forename: Julie Y
authors.initials: JY
authors.lastname: Zhou
authors.forename: Nermina
authors.initials: N
authors.lastname: Topcagic
authors.forename: Brian T
authors.initials: BT
authors.lastname: Edelson
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Ferkol
authors.forename: Megan A
authors.initials: MA
authors.lastname: Cooper
authors.forename: Jared T
authors.initials: JT
authors.lastname: Muenzer
authors.forename: Sharon Celeste
authors.initials: SC
authors.lastname: Morley
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism*; D011018:Pneumonia, Pneumococcal / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C026742:plastin; C064658:RAG-1 protein