Genetic labeling reveals altered turnover and stability of innate lymphocytes in latent mouse cytomegalovirus infection

TY - JOUR

T1 - Genetic labeling reveals altered turnover and stability of innate lymphocytes in latent mouse cytomegalovirus infection

AU - Busche, Andreas

AU - Schmitz, Susanne

AU - Fleige, Henrike

AU - Robbins, Scott H

AU - Walzer, Thierry

AU - Stewart, Charles A

AU - Förster, Reinhold

AU - Messerle, Martin

AU - Prinz, Immo

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Mouse CMV (MCMV) infection rapidly induces the proliferation of NK cells, which correlates with immunological protection. Whether NK cells primed during acute response against MCMV are maintained for the long term is not known. In this study, we used TcrdH2BeGFP mice in which maturing NK cells are genetically labeled with a pulse of very stable histone-2B-eGFP. In this system, we found that the reporter protein was diluted out upon NK cell division during acute MCMV infection. At the same time, mature NK cells in uninfected mice showed only very limited turnover in vivo. Three months after primary infection when MCMV latency was established, the majority of peripheral NK cells still displayed a higher record of proliferation than NK cells in mock-infected controls. This observation included both Ly49H(+) and Ly49H(-) NK cells. Conversely, naive NK cells did not show more proliferation after transfer into latently MCMV-infected mice than that after transfer into mock-infected control mice. This indicated that the observed alterations of the NK cell compartment in MCMV latency were "legacy" (i.e., resulting from prior events during the initial immune response). Together, these results suggest that antiviral immune responses induce sustained alterations of innate lymphocyte populations that extend far beyond the first days of acute infection.

AB - Mouse CMV (MCMV) infection rapidly induces the proliferation of NK cells, which correlates with immunological protection. Whether NK cells primed during acute response against MCMV are maintained for the long term is not known. In this study, we used TcrdH2BeGFP mice in which maturing NK cells are genetically labeled with a pulse of very stable histone-2B-eGFP. In this system, we found that the reporter protein was diluted out upon NK cell division during acute MCMV infection. At the same time, mature NK cells in uninfected mice showed only very limited turnover in vivo. Three months after primary infection when MCMV latency was established, the majority of peripheral NK cells still displayed a higher record of proliferation than NK cells in mock-infected controls. This observation included both Ly49H(+) and Ly49H(-) NK cells. Conversely, naive NK cells did not show more proliferation after transfer into latently MCMV-infected mice than that after transfer into mock-infected control mice. This indicated that the observed alterations of the NK cell compartment in MCMV latency were "legacy" (i.e., resulting from prior events during the initial immune response). Together, these results suggest that antiviral immune responses induce sustained alterations of innate lymphocyte populations that extend far beyond the first days of acute infection.

KW - Acute Disease

KW - Animals

KW - Cytomegalovirus Infections/immunology

KW - Green Fluorescent Proteins/genetics

KW - Histones/genetics

KW - Immunity, Innate/genetics

KW - Killer Cells, Natural/immunology

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Muromegalovirus/genetics

KW - NK Cell Lectin-Like Receptor Subfamily A/biosynthesis

KW - Virus Latency/genetics

U2 - 10.4049/jimmunol.1003232

DO - 10.4049/jimmunol.1003232

M3 - SCORING: Journal article

C2 - 21270406

VL - 186

SP - 2918

EP - 2925

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 5

ER -