title: Innate immune reconstitution with suppression of HIV-1.
abstract: 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 theTNFApromoter 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.
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Scully
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Ainsley
authors.initials: A
authors.lastname: Lockhart
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Wilfredo
authors.initials: W
authors.lastname: Garcia-Beltran
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Christine D
authors.initials: CD
authors.lastname: Palmer
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Chelsey
authors.initials: C
authors.lastname: Musante
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Rosenberg
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
authors.forename: J Judy
authors.initials: JJ
authors.lastname: Chang
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA; Heinrich-Pette-Institut, Hamburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld