Massachusetts General Hospital
AIDS Rsearch, 149-5
149 13th Street
Charlestown, MA 02129
The interests of my laboratory are focused on targeting innate immune responses to gain more effective control of chronic human viral infections, including HIV and HCV. The innate immune response serves as our body’s first line defense against foreign pathogens and tumors. While we have learnt to effectively modulate the innate immune response immediately following vaccination, much less is known about mechanisms to target the antiviral properties of innate immune cells directly to virally infected cells for a prolonged period of time following vaccination. Understanding how one could provide long-term specificity to innate immune cells and target them to specific tissues, where they may play a central role in capturing the incoming virus, potentially providing a more aggressive first line defense against these incoming pathogens and may allow the adaptive immune response to go on and clear the infection more aggressively.
The paradox: How does one provide specificity to non-specific innate immune cells? All innate immune cells express Fc-receptors, which bind to antibodies. Since antibodies are antigen specific, the induction of antibodies that can effectively bind to Fc-receptors, and recruit innate effector function, may provide innate immune cells with specificity for infected cells. Our group studies the range of innate immune responses that can be elicited by antibodies in both natural infection as well as following vaccination. Furthermore, understanding the mechanism by which antibodies interact with different Fc-receptors in various tissues to induce the most protective antiviral functions may provide us with critical new insights into potential new therapeutic strategies that can be targeted through vaccination to gain more effective control over chronic viral infections.
1. Alter G, Martin M, Teigen N, Carr W, Suscovich T, Schneidewind A, Streeck H, Waring MT, Meier A, Brander B, Lifson J, Allen T, Carrington M, Altfeld M.. Differential Natural Killer cell mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes. J Exp Med. 2007 Nov 26;204(12):3027-36.
2. Alter G, Suzannah Rihn, Katharine Walters, Anne Nolting, Maureen Martin, Eric S. Rosenberg, Jeffrey S. Miller, Mary Carrington, and Marcus Altfeld HLA class I subtype dependent expansion of KIR3DS1+ and KIR3DL1+ NK cells during acute HIV-1 infection J Virol. 2009 Jul;83(13):6798-805.
3. Liu Q, Sun Y, Rihn S, Nolting A, Tsoukas PN, Jost S, Cohen K, Walker B, Alter G. Matrix Metalloprotease inhibitors restore impaired NK cell mediated Antibody dependent cellular cytotoxicity in human immunodeficiency virus-1 infection. J Virol. 2009 Jun 24.
Last Update: 1/6/2014