Faculty
 |
Gary B. Huffnagle |
Our laboratory is interested in understanding how immune responses to infectious agents develop in vivo. Animal models of infection allow the identification and dissection of complex immune signaling networks that are often not predicted from in vitro studies. As an example, we have recently identified that expression of CCR2, a receptor for a number of chemotactic cytokines (chemokines), is critically required for the development of protective T1 cell-mediated immunity against pulmonary fungal infection. In the absence of CCR2, mice develop a non-protective T2 ("allergic") response. Thus, CCR2 plays an important role in the development of T cell immunity in vivo, in addition to its role in leukocyte hemotaxis/recruitment. CCR5 is also a chemokine receptor, but CCR5 plays an organ-specific role in recruitment during infection. We are also studying the role of innate immunity (e. g. TNFa and chemokines such as MCP-1 and MIP-1a) in the development of T1 vs. T2 immunity in the lungs.
Our laboratory also studies how virulence factors produced by microbes can alter the cellular microenvironment in which microbial antigens are recognized (i. e. microbes are "dynamic antigens"). We are utilizing a mouse model of pulmonary cryptococcosis (a fungal infection) and bacterial pneumonia to study the interplay between cytokines/cells of the immune system and microbial virulence factors. We have also recently begun to generate cytokine-expressing gene therapy vectors to explore how immune responses to infectious agents can be augmented by this immuno-therapeutic approach.
Selected Publications:
Huffnagle GB, McNeil LK, McDonald RA, Murphy JW, Toews GB, Maeda N, Kuziel WA. Cutting Edge: Role of CCR5 in organ-specific and innate immunity to Cryptococcus neoformans. J Immunol 1999, 163: 4642-4646.
Traynor TR, Kuziel WA, Toews GB, Huffnagle GB. CCR2 expression determines T1 vs. T2 polarization during pulmonary Cryptococcus neoformans infection. J Immunol 2000, 164(4):2021-2027.
Aliberti J, Reis e Sousa C, Schito M, Hieny S, Wells T, Huffnagle GB, Sher A. CCR5 provides a signal for microbial induced production of IL-12 by CD8a+ dendritic cells. Nature Immunol 2000, 1:83-87.
Olszewski MA, Huffnagle GB, McDonald RA, Lindell DM, Cook DN, Toews GB. The role of MIP-1a/CCL3 in regulation of T cell-mediated immunity to Cryptococcus neoformans infection. J Immunol 2000, 165(11):6429-36.
Noverr MC, Phare SM, Toews GB, Coffey MJ, Huffnagle GB. Production of immunomodulatory prostaglandins by the pathogenic yeast Cryptococcus neoformans and Candida albicans. Infect Immun 2001 (in press).
