NDLI: Dynamic roles of type I and type II IFNs in early infection with Mycobacterium tuberculosis.

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Dynamic roles of type I and type II IFNs in early infection with Mycobacterium tuberculosis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wolf, Andrea J. Ernst, Joel D. Desvignes, Ludovic
Description	Country affiliation: United States Author Affiliation: Desvignes L ( Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.)
Abstract	Although the protective role of type II IFN, or IFN-Î³, against Mycobacterium tuberculosis has been established, the effects of type I IFNs are still unclear. One potential confounding factor is the overlap of function between the two signaling pathways. We used mice carrying null mutations in the type I IFNR, type II IFNR, or both and compared their immune responses to those of wild-type mice following aerosol infection with M. tuberculosis. We discovered that, in the absence of a response to IFN-Î³, type I IFNs play a nonredundant protective role against tuberculosis. Mice unable to respond to both types of IFNs had more severe lung histopathology for similar bacterial loads and died significantly earlier than did mice with impaired IFN-Î³ signaling alone. We excluded a role for type I IFN in T cell recruitment, which was IFN-Î³ dependent, whereas both types of IFNs were required for optimal NK cell recruitment to the lungs. Type I IFN had a time-dependent influence on the composition of lung myeloid cell populations, in particular by limiting the abundance of M. tuberculosis-infected recruited macrophages after the onset of adaptive immunity. We confirmed that response to IFN-Î³ was essential to control intracellular mycobacterial growth, without any additional effect of type I IFN. Together, our results imply a model in which type I IFN limit the number of target cells that M. tuberculosis can infect in the lungs, whereas IFN-Î³ enhances their ability to restrict bacterial growth.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1200255
Journal	The Journal of Immunology
Issue Number	12
Volume Number	188
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Interferon Type I Immunology Interferon-gamma Tuberculosis, Pulmonary Animals Cytokines Biosynthesis Enzyme-linked Immunosorbent Assay Flow Cytometry Mice Mice, Inbred C57bl Mice, Knockout Mycobacterium Tuberculosis Microbiology Pathology Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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