Priming of the Respiratory Tract with Immunobiotic Lactobacillus plantarum Limits Infection of Alveolar Macrophages with Recombinant Pneumonia Virus of Mice (rK2-PVM)

• Authors: Kimberly D. Dyer, National Institute of Allergy and Infectious Diseases; Rebecca A. Drummond, National Institute of Allergy and Infectious Diseases; Tyler A. Rice, National Institute of Allergy and Infectious Diseases; Caroline M. Percopo, National Institute of Allergy and Infectious Diseases; Todd A. Brenner, National Institute of Allergy and Infectious Diseases; Derek A.G. Barisas, National Institute of Allergy and Infectious Diseases; Kendel A. Karpe, National Institute of Allergy and Infectious Diseases; Martin Moore, Emory University; Helene F. Rosenberg, National Institute of Allergy and Infectious Diseases
• Journal Title: Journal of Virology
• Volume: Volume 90, Number 2
• Publisher: American Society for Microbiology | 2016-01-01, Pages 979-991
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1128/JVI.02279-15
• Subjects: Biology, Virology; Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Virology; LETHAL PNEUMOVIRUS INFECTION; INFLUENZA-A VIRUS; MOUSE LUNG-TISSUE; SYNCYTIAL VIRUS; DENDRITIC CELLS; T-CELLS; REVERSE GENETICS; INNATE IMMUNITY; HOST-DEFENSE; DISEASE

Abstract

Pneumonia virus of mice (PVM) is a natural rodent pathogen that replicates in bronchial epithelial cells and reproduces many clinical and pathological features of the more severe forms of disease associated with human respiratory syncytial virus. In order to track virus-target cell interactions during acute infection in vivo, we developed rK2-PVM, bacterial artificial chromosomebased recombinant PVM strain J3666 that incorporates the fluorescent tag monomeric Katushka 2 (mKATE2). The rK2-PVM pathogen promotes lethal infection in BALB/c mice and elicits characteristic cytokine production and leukocyte recruitment to the lung parenchyma. Using recombinant virus, we demonstrate for the first time PVM infection of both dendritic cells (DCs; CD11c+ major histocompatibility complex class II+) and alveolar macrophages (AMs; CD11c+ sialic acid-binding immunoglobulin- like lectin F+) in vivo and likewise detect mKATE2+ DCs in mediastinal lymph nodes from infected mice. AMs support both active virus replication and production of infectious virions. Furthermore, we report that priming of the respiratory tract with immunobiotic Lactobacillus plantarum, a regimen that results in protection against the lethal inflammatory sequelae of acute respiratory virus infection, resulted in differential recruitment of neutrophils, DCs, and lymphocytes to the lungs in response to rK2-PVM and a reduction from ~ 40% to <10% mKATE2+ AMs in association with a 2-log drop in the release of infectious virions. In contrast, AMs from L. plantarum-primed mice challenged with virus ex vivo exhibited no differential susceptibility to rK2-PVM. Although the mechanisms underlying Lactobacillus-mediated viral suppression remain to be fully elucidated, this study provides insight into the cellular basis of this response.