Bidirectional Natural Killer Cell and Dendritic Cell Interactions in HIV-1 Pathogenesis

Natural killer (NK) and dendritic cell (DC) interactions are pivotal for the development of immune responses, which lead to bidirectional NK:DC activation. In HIV-1 infection, both NK cell and DC function are impaired, resulting in dysfunctional NK:DC crosstalk. We demonstrate that NK:DC interactions result in the induction of CD4 expression on NK cells, thereby increasing NK cell susceptibility to HIV-1 infection. Furthermore, we show that NK:DC interactions influence NK cell degranulation.CD4+ NK cells mediate DC maturation via cell-cell contact interactions and soluble factors. We find that CD4+ NK cells are more efficient at inducing DC maturation than CD4- NK cells, suggesting that CD4 is an activation marker on NK cells. CD4+ NK cells also influence DC function as they decrease DC macropinocytotic capacity, which is characteristic of DC maturation. NK:DC interactions affect HIV-1 infection, as NK-mature DCs effectively deliver HIV-1 to T cells via trans-infection. DC-mediated induction of CD4 expression on NK cells renders NK cells susceptible to HIV-1 infection. Furthermore, DCs can transfer infectious viruses and enhance HIV-1 infection of CD4+ NK cells.Our findings provide new insights regarding NK:DC interactions, defining a mechanism by which cellular interactions in the absence of pathogens promote DC-mediated amplification of HIV-1 infection. These findings provide a new mechanism by which CD4 expression can be induced in vivo, resulting in HIV-1 infection of NK cells.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Molecular Biology and Microbiology

Grantor dc:publisher

Case Western Reserve University School of Graduate Studies

Year dc:date

2013

Author dc:creator

• Valentin-Torres, Alice M.

Contributors dc:contributor

• Bernstein, Helene
• McDonald, David

• Immunology
• Molecular Biology
• Virology
• HIV
• NK cell
• Dendritic Cells
• bidirectional interactionsi

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=case1346268879

OAI identifier oai:identifier

oai:etd.ohiolink.edu:case1346268879