Innate immune reconstitution with suppression of HIV-1

被引:10
作者
Scully, Eileen P. [1 ,2 ]
Lockhart, Ainsley [1 ]
Garcia-Beltran, Wilfredo [1 ]
Palmer, Christine D. [1 ]
Musante, Chelsey [1 ]
Rosenberg, Eric [3 ]
Allen, Todd M. [1 ]
Chang, J. Judy [1 ,6 ]
Bosch, Ronald J. [4 ]
Altfeld, Marcus [1 ,5 ]
机构
[1] Ragon Inst Massachusetts Gen Hosp Massachusetts I, 400 Technol Sq, Cambridge, MA 20139 USA
[2] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA
[3] Massachusetts Gen Hosp, Boston, MA 02114 USA
[4] Harvard Sch Publ Hlth, Boston, MA USA
[5] Heinrich Pette Inst, Martinistrase52, Hamburg, Germany
[6] Univ Melbourne, Doherty Inst Infect & Immun, Melbourne, Vic, Australia
关键词
IMMUNODEFICIENCY-VIRUS VIREMIA; SINGLE-STRANDED RNA; ANTIRETROVIRAL THERAPY; DENDRITIC CELLS; IN-VIVO; INFLAMMATORY SYNDROME; MONOCYTE SUBSET; C VIRUS; INFECTION; ACTIVATION;
D O I
10.1172/jci.insight.85433
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Progressive HIV-1 infection leads to both profound immune suppression and pathologic inflammation in the majority of infected individuals. While adaptive immune dysfunction, as evidenced by CD4(+) T cell depletion and exhaustion, has been extensively studied, less is known about the functional capacity of innate immune cell populations in the context of HIV-1 infection. Given the broad susceptibility to opportunistic infections and the dysregulated inflammation observed in progressive disease, we hypothesized that there would be significant changes in the innate cellular responses. Using a cohort of patients with multiple samplings before and after antiretroviral therapy (ART) initiation, we demonstrated increased responses to innate immune stimuli following viral suppression, as measured by the production of inflammatory cytokines. Plasma viral load itself had the strongest association with this change in innate functional capacity. We further identified epigenetic modifications in the TNFA promoter locus in monocytes that are associated with viremia, suggesting a molecular mechanism for the observed changes in innate immune function following initiation of ART. These data indicate that suppression of HIV-1 viremia is associated with changes in innate cellular function that may in part determine the restoration of protective immune responses.
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页数:14
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