title: Defective dendritic cell response to Toll-like receptor 7/8 agonists in perinatally HIV-infected children.
abstract: Understanding the defects in innate immunity associated with perinatal HIV infection is a prerequisite for effective antiretroviral treatment. We therefore compared the innate immune response [dendritic cell (DC) phenotype and function] in peripheral blood by flow cytometry at baseline and 12 months in HIV-infected children to determine the defect associated with perinatal HIV infection. As compared with controls, patients had decreased numbers of total DCs including plasmacytoid (p)DCs and myeloid (m)DCs and impaired function based on induction of maturation markers (CD83, CD80, CCR7) and cytokines tumor necrosis factor-α and interferon-α (exclusive to pDC) upon stimulation with the TLR7/8 agonist Resiquimod. These abnormalities were evident in all three CD4 immune categories and persisted over 12 months; pDC function worsened in HIV+ children without treatment and improved slightly in those on highly active antiretroviral therapy (HAART). In conclusion, a majority of perinatally HIV-infected older children without HAART remain clinically stable in the short term, but have demonstrable immunologic abnormalities indicative of defects in the innate immune system. Children initiated on HAART showed improvement in CD4 counts but did not show improvement in DC function over the short term.
authors.affiliation: Department of Clinical Research, National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chennai, India.
authors.forename: Anbalagan
authors.initials: A
authors.lastname: Selvaraj
authors.forename: Sudheesh
authors.initials: S
authors.lastname: Pilakka-Kanthikeel
authors.forename: Perumal Kannabiran
authors.initials: PK
authors.lastname: Bhavani
authors.forename: Luke E
authors.initials: LE
authors.lastname: Hanna
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
mesh_terms: D000293:Adolescent; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism* / Q000635:transmission / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007223:Infant; D008297:Male; D012307:Risk Factors; D013997:Time Factors; D051199:Toll-Like Receptor 7 / Q000819:agonists*; D051200:Toll-Like Receptor 8 / Q000819:agonists*; D019562:Viral Load
chemical_list: D016207:Cytokines; D007093:Imidazoles; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C402365:resiquimod
keywords: dendritic cells; innate immunity; pediatric HIV