Early resolution of acute immune activation and induction of PD-1 in SIV-infected sooty mangabeys distinguishes nonpathogenic from pathogenic infection in rhesus macaques.
Primate lentiviruses are typically apathogenic in their evolutionarily coadapted host species but can be lethal when transferred to new host species. Why such infections are pathogenic in humans and rhesus macaques (RMs) but not in sooty mangabeys (SMs), a natural host, remains unclear. Studies of chronically infected animals point to the importance of diminished immune activation in response to the infection in SMs. In this study, we sought the causes and timing of the differences in immune activation in a comparative study of acute SIV infection in RMs and SMs. Surprisingly, we show that in acute infection immune activation is comparable in SMs and RMs but thereafter, SMs quickly resolve immune activation, whereas RMs did not. Early resolution of immune activation in SMs correlated with increased expression of PD-1 and with preservation of CD4(+) T cell counts and lymphatic tissue architecture. These findings point to early control of immune activation by host immunoregulatory mechanisms as a major determinant of the different disease outcomes in SIV infection of natural vs non-natural hosts.
Estes
Jacob D
JD
Department of Microbiology, Medical School, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA.
Gordon
Shari N
SN
Zeng
Ming
M
Chahroudi
Ann M
AM
Dunham
Richard M
RM
Staprans
Silvija I
SI
Reilly
Cavan S
CS
Silvestri
Guido
G
Haase
Ashley T
AT
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016665:Cercocebus atys / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology; D008992:Monkey Diseases / Q000276:immunology* / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity*
D000943:Antigens, Differentiation