Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes

218Citations
Citations of this article
236Readers
Mendeley users who have this article in their library.

Abstract

Type I interferons (IFNs) are important for host defense from viral infections, acting to restrict viral production in infected cells and to promote antiviral immune responses. However, the type I IFN system has also been associated with severe lung inflammatory disease in response to respiratory syncytial virus (RSV). Which cells produce type I IFNs upon RSV infection and how this directs immune responses to the virus, and potentially results in pathological inflammation, is unclear. Here, we show that alveolar macrophages (AMs) are the major source of type I IFNs upon RSV infection in mice. AMs detect RSV via mitochondrial antiviral signaling protein (MAVS)-coupled retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs), and loss of MAVS greatly compromises innate immune restriction of RSV. This is largely attributable to loss of type I IFN-dependent induction of monocyte chemoattractants and subsequent reduced recruitment of inflammatory monocytes (infMo) to the lungs. Notably, the latter have potent antiviral activity and are essential to control infection and lessen disease severity. Thus, infMo recruitment constitutes an important and hitherto underappreciated, cell-extrinsic mechanism of type I IFN-mediated antiviral activity. Dysregulation of this system of host antiviral defense may underlie the development of RSV-induced severe lung inflammation.

References Powered by Scopus

Monocyte chemoattractant protein-1 (MCP-1): An overview

3013Citations
N/AReaders
Get full text

Monocyte recruitment during infection and inflammation

2281Citations
N/AReaders
Get full text

Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2

1349Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice

1183Citations
N/AReaders
Get full text

Shared and Distinct Functions of Type I and Type III Interferons

773Citations
N/AReaders
Get full text

IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes

427Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Goritzka, M., Makris, S., Kausar, F., Durant, L. R., Pereira, C., Kumagai, Y., … Johansson, C. (2015). Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes. Journal of Experimental Medicine, 212(5), 699–714. https://doi.org/10.1084/jem.20140825

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 103

69%

Researcher 31

21%

Professor / Associate Prof. 15

10%

Lecturer / Post doc 1

1%

Readers' Discipline

Tooltip

Immunology and Microbiology 65

40%

Agricultural and Biological Sciences 54

33%

Biochemistry, Genetics and Molecular Bi... 23

14%

Medicine and Dentistry 22

13%

Save time finding and organizing research with Mendeley

Sign up for free