NDLI: Dissecting the contribution of IgG subclasses in restricting airway infection with Legionella pneumophila.

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Dissecting the contribution of IgG subclasses in restricting airway infection with Legionella pneumophila.

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Dissecting the contribution of IgG subclasses in restricting airway infection with Legionella pneumophila.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Weber, Stefan S. Ducry, Jasmin Oxenius, Annette
Description	Country affiliation: Switzerland Author Affiliation: Weber SS ( Institute of Microbiology, Swiss Federal Institute of Technology Zürich, CH-8093 Zürich, Switzerland.); Ducry J ( Institute of Microbiology, Swiss Federal Institute of Technology Zürich, CH-8093 Zürich, Switzerland.); Oxenius A ( Institute of Microbiology, Swiss Federal Institute of Technology Zürich, CH-8093 Zürich, Switzerland aoxenius@micro.biol.ethz.ch.)
Abstract	Abs are able to mediate local protection from pulmonary infection with Legionella pneumophila, the causative agent of a severe form of pneumonia known as Legionnaires' disease. L. pneumophila is able to infect alveolar macrophages in the lung and replicates intracellularly in a vacuolar compartment with endoplasmic reticulum-like characteristics. However, Abs opsonize the bacteria and confer an FcR-mediated signal to phagocytic host cells that vetoes the bacterial evasion strategies, thereby efficiently targeting the bacteria to intracellular lysosomal degradation. In this study we analyzed the prevalence of pathogen-specific IgG subclasses present in immunized mice and found that the presence of IgG2c and IgG3 correlated with reduced bacterial titers after intranasal infection. We then isolated different IgG subclasses and compared their differential prophylactic potential in restricting airway L. pneumophila replication. We found that all IgG subclasses were effective in restricting pulmonary airway infection in mice when administered at high and equivalent doses. However, at limiting Ab concentrations we found a superior role of IgG2c in restricting L. pneumophila replication in a prophylactic setting. Furthermore, we assessed the therapeutic efficacy of administering an mAb during an established infection and found that bacterial titers could be reduced very efficiently with such a treatment. Thus, we propose the therapeutic use of Abs for the treatment of intracellular bacterial infections in situations where antibiotics might be ineffective.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-10-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibodies, Bacterial Therapeutic Use Antibodies, Monoclonal Immunoglobulin G Legionella Pneumophila Legionnaires' Disease Therapy Animals Administration & Dosage Immunology Cells, Cultured Hek293 Cells Classification Immunotherapy Microbiology Lipopolysaccharides Macrophages, Alveolar Mice Mice, Inbred C57bl Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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