Altered dendritic cellnatural killer interaction in Kenyan sex workers resistant to HIV-1 infection

Ghadially, Hormasa,b; Keynan, Yoavc,d; Kimani, Joshuac,d; Kimani, Makobud; Ball, T. Blakec,d,e; Plummer, Francis A.c,d,f; Mandelboim, Ofera; Meyers, Adrienne F.A.c,d,e

AIDS:
doi: 10.1097/QAD.0b013e32834f98ea
Basic Science
Abstract

Background: Natural killer (NK) cells are members of the innate immune system that play an important role in the defense against viral infection. They are also involved in the regulation of adaptive immune responses through cytokine secretion and the interaction with antigen-presenting cells. However, their role in HIV infection is only partially understood.

Objective: Here we studied the phenotype and function of NK cells of highly HIV-exposed but seronegative (HESN) uninfected commercial sex workers from Kenya who can be epidemiologically defined as relatively resistant to HIV infection.

Design: The purpose of this study was to gain insight into the role of NK cells in mediating resistance to HIV-1. This information can be used to better understand protection from infection which can be used for informing future design of effective prophylactics and therapeutics for HIV.

Methods: Whole blood samples were collected from study participants and isolated NK cells and dendritic cells were used in assays for phenotyping and cell function.

Results: Activated NK cells from resistant women killed autologous immature dendritic cells more efficiently and also secreted more interferon (IFN)-γ than those of uninfected, susceptible women. Interestingly, NK cells from HIV-resistant women were significantly more effective in inducing secretion of IL-12 in immature dendritic cells.

Conclusions: These data suggest that an altered NK cell–dendritic cell interaction plays an important role in the protection from infection with HIV-1.

Author Information

aThe Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem, Israel

bMedImmune Limited, Granta Park, Cambridge, UK

cDepartment of Medical Microbiology, University of Manitoba, Winnipeg, Canada

dDepartment of Medical Microbiology, University of Nairobi, Nairobi, Kenya

eNational HIV and Retrovirology Laboratories

fNational Microbiology Lab, Public Health Agency of Canada, Winnipeg, Canada.

Correspondence to Adrienne Meyers, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg MB R3E 3R2, Canada. E-mail: Adrienne.Meyers@phac-aspc.gc.ca

Received 10 August, 2011

Revised 31 October, 2011

Accepted 23 November, 2011

© 2012 Lippincott Williams & Wilkins, Inc.