Impaired restoration of plasmacytoid dendritic cells in HIV-1-infected patients with poor CD4 T cell reconstitution is associated with decrease in capacity to produce IFN-alpha but not proinflammatory cytokines.
We analyzed reconstitution characteristics of plasmacytoid dendritic cells (PDCs) and myeloid DCs-1 in 38 HIV-1-infected patients with impaired restoration of CD4 T cell counts despite prolonged suppression of plasma viremia (discordant) and compared them with 42 patients showing good immunological and virological responses following highly active antiretroviral therapy (HAART). While myeloid DCs showed spontaneous recovery following HAART in both the groups, the discordant patients demonstrated poor peripheral reconstitution of PDCs as compared with concordant patients. The ability of PDCs to produce IFN-alpha following stimulation with TLR7 ligand imiquimod and TLR9 ligand CpG ODN-2216 was also impaired in discordant patients even after 2 years following initiation of HAART. Lower IFN-alpha expression in the PDCs following TLR stimulation was further associated with lower expression of transcription factor, IFN regulatory factor-7. In contrast, production of TNF-alpha and IL-6 following TLR stimulation was comparable in both groups of patients, indicating that impaired reconstitution characteristics do not affect the capacity of PDCs to produce proinflammatory cytokines. The discordant patients had significantly lower baseline CD4 T cell counts and higher baseline viral load at the initiation of HAART implying that lower baseline CD4 T cell counts and higher plasma viral load are associated with impaired restoration of CD4 T cells and PDCs, thus, increasing the susceptibility of discordant patients toward opportunistic infections despite virological control.
Sachdeva
Naresh
N
Laboratory for Clinical and Biological Studies, University of Miami-Miller School of Medicine, Miami, FL 33136, USA.
Asthana
Vishwaratn
V
Brewer
Toye H
TH
Garcia
Deborah
D
Asthana
Deshratn
D
D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000096:biosynthesis; D019562:Viral Load
D016207:Cytokines; D018836:Inflammation Mediators; D016898:Interferon-alpha; D012367:RNA, Viral