Pilot Project

Mark Lang, Ph.D.

Anthrax toxin-induced anergy in primary human NKT cells

The bacterium Bacillus anthracis is the causative agent of anthrax infection. Anthrax is a life-threatening disease caused by inhalation or ingestion of spores, or transmission through wounds and abrasions. The bacterium secretes toxins, proteins that enter numerous cell types in an infected individual altering their function and contributing to the disease process. Consequently, we and other researchers are dedicated to identifying cells affected by anthrax toxins and to understanding the implications for the function of those cells. We have observed that anthrax toxins adversely affect a type of cell in the immune system known as a natural killer-like T (NKT) cell. NKT cells are found in the bone marrow, blood, spleen, lymph nodes and liver and are required for optimal immune responses. We report that anthrax toxins effectively shut down NKT cells, preventing them from functioning normally. We propose that this has serious consequences because anyone infected with Bacillus anthracis will be less able to mount an immune response against it.

 
Devera TS, Joshi SK, Aye LM, Lang GA, Ballard JD, Lang ML. Regulation of anthrax toxin-specific antibody titers by natural killer T cell-derived IL-4 and IFNgamma. PLoS One 6:e23817, 2011. [Abstract]

Devera TS, Aye LM, Lang GA, Joshi SK, Ballard JD, Lang ML. CD1d-dependent B-cell help by NK-like T cells leads to enhanced and sustained production of Bacillus anthracis lethal toxin-neutralizing antibodies. Infect Immun 78:1610-1617, 2010. [Abstract]

Joshi SK, Lang GA, Larabee JL, Devera TS, Aye LM, Shah HB, Ballard JD, Lang ML. Bacillus anthracis lethal toxin disrupts TCR signaling in CD1d-restricted NKT cells leading to functional anergy. PLoS Pathog 5:e1000588, 2009. [Abstract]