pDC in HIV infection

Dr. Manches is interested in the role of plasmacytoid dendritic cells (pDC) in HIV infection. pDC are crucial cells in virus infection, as they secrete high amounts of type I interferon with potent anti-viral activity. They can also function as antigen-presenting cells, although less efficiently than conventional dendritic cells. Both of these functions, IFNalpha  secretion, and antigen presentation, have potential beneficial and detrimental role in HIV infection. Thus, although type I interferon is associated with resistance to viral infection, chronic IFNalpha secretion probably contributes to immune activation and immune system exhaustion in chronic disease.

How type I interferon is regulated in HIV is not completely understood. In collaboration with Dr. O’Brien, Dr. Manches is investigating the cellular and molecular mechanisms by which IFNalpha is regulated upon infection by HIV and other viral or bacterial pathogens, with the aim to understand and manipulate type I interferon secretion in pDC during acute and chronic infection.

pDC can also function as antigen-presenting cells. The outcome of antigen presentation by pDC is complex and context dependent. This lab and others have shown that pDC can induce the differentiation and activation of regulatory T cells (Treg). Treg can inhibit anti-HIV immune responses, but also potentially dampen the damaging immune activation observed in chronic HIV infection. He is investigating the molecular mechanisms through which pDC induce the differentiation of Treg.

Olivier Manches, PhD, Assistant Professor

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