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Defective dendritic cell response to Toll-like receptor 7/8 agonists in perinatally HIV-infected children

Anbalagan Selvaraj1, Sudheesh Pilakka-Kanthikeel, Perumal Kannabiran Bhavani

  • 1Department of Clinical Research, National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chennai, India.

Pathogens and Disease
|July 23, 2013
PubMed

Insights

Perinatal HIV infection impairs innate immunity, causing defects in dendritic cell (DC) numbers and function. Highly active antiretroviral therapy (HAART) improves CD4 counts but not DC function in children.

Area of Science:

  • Immunology
  • Virology
  • Pediatrics

Background:

  • Perinatal HIV infection can lead to significant immune system defects.
  • Understanding innate immunity is crucial for developing effective antiretroviral treatments.

Purpose of the Study:

  • To compare the innate immune response, specifically dendritic cell (DC) phenotype and function, in HIV-infected children.
  • To identify immune defects associated with perinatal HIV infection.

Main Methods:

  • Peripheral blood samples were analyzed using flow cytometry at baseline and 12 months.
  • Dendritic cell (DC) numbers, maturation markers (CD83, CD80, CCR7), and cytokine production (TNF-α, IFN-α) were assessed.
  • Cells were stimulated with the TLR7/8 agonist Resiquimod.

Main Results:

  • HIV-infected children had reduced numbers of total DCs, including plasmacytoid (pDCs) and myeloid DCs (mDCs).
  • DC function was impaired, with reduced maturation marker and cytokine induction.
  • These abnormalities persisted for 12 months and were present across all CD4 immune categories.
  • pDC function worsened in untreated HIV+ children and slightly improved with highly active antiretroviral therapy (HAART).

Conclusions:

  • Perinatally HIV-infected children without HAART exhibit persistent innate immune system defects despite short-term clinical stability.
  • Initiation of HAART improved CD4 counts but did not significantly enhance DC function in the short term.

Keywords:
dendritic cellsinnate immunitypediatric HIV

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