Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12

Orr-El Weizman; Eric Song; Nicholas M Adams; Andrew D Hildreth; Luke Riggan; Chirag Krishna; Oscar A Aguilar; Christina S Leslie; James R Carlyle; Joseph C Sun; Timothy E O'Sullivan

doi:10.1038/s41590-019-0430-1

Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12

Nat Immunol. 2019 Aug;20(8):1004-1011. doi: 10.1038/s41590-019-0430-1. Epub 2019 Jul 1.

Authors

Orr-El Weizman^{1

2}, Eric Song², Nicholas M Adams^{1

3}, Andrew D Hildreth^{4

5}, Luke Riggan^{4

5}, Chirag Krishna⁶, Oscar A Aguilar^{7

8}, Christina S Leslie⁶, James R Carlyle⁷, Joseph C Sun^{1

3

9}, Timothy E O'Sullivan^{10

11}

Affiliations

¹ Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
² Department of Immunobiology, Yale University, New Haven, CT, USA.
³ Louis V. Gerstner Jr, Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴ Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷ Department of Immunology, University of Toronto, Toronto, Canada.
⁸ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
⁹ Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA.
¹⁰ Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA. tosullivan@mednet.ucla.edu.
¹¹ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA. tosullivan@mednet.ucla.edu.

Abstract

Innate lymphoid cells (ILCs) are tissue-resident sentinels that are essential for early host protection from pathogens at initial sites of infection. However, whether pathogen-derived antigens directly modulate the responses of tissue-resident ILCs has remained unclear. In the present study, it was found that liver-resident type 1 ILCs (ILC1s) expanded locally and persisted after the resolution of infection with mouse cytomegalovirus (MCMV). ILC1s acquired stable transcriptional, epigenetic and phenotypic changes a month after the resolution of MCMV infection, and showed an enhanced protective effector response to secondary challenge with MCMV consistent with a memory lymphocyte response. Memory ILC1 responses were dependent on the MCMV-encoded glycoprotein m12, and were independent of bystander activation by proinflammatory cytokines after heterologous infection. Thus, liver ILC1s acquire adaptive features in an MCMV-specific manner.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Herpesviridae Infections / immunology
Herpesviridae Infections / virology
Immunity, Innate / immunology
Immunologic Memory / immunology*
Interleukin-18 Receptor alpha Subunit / metabolism
Liver / cytology
Liver / immunology*
Lymphocytes / immunology*
Membrane Glycoproteins / immunology*
Mice
Muromegalovirus / immunology*
Viral Envelope Proteins / immunology*

Substances

IL18R1 protein, human
Interleukin-18 Receptor alpha Subunit
M12 protein, Mouse mammary tumor virus
Membrane Glycoproteins
Viral Envelope Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding