Ingestion of Bacillus anthracis spores causes gastrointestinal (GI) anthrax. Humoral immune responses, particularly immunoglobulin A (IgA)-secreting B-1 cells, play a critical role in the clearance of GI pathogens. Here, we investigated whether B. anthracis impacts the function of colonic B-1 cells to establish active infection. GI anthrax led to significant inhibition of immunoglobulins (eg, IgA) and increased expression of program death 1 on B-1 cells. Furthermore, infection also diminished type 2 innate lymphoid cells (ILC2) and their ability to enhance differentiation and immunoglobulin production by secreting interleukin 5 (IL-5). Such B-1-cell and ILC2 dysfunction is potentially due to cleavage of p38 and Erk1/2 mitogen-activated protein kinases in these cells. Conversely, mice that survived infection generated neutralizing antibodies via the formation of robust germinal center B cells in Peyer's patches and had restored B-1-cell and ILC2 function. These data may provide additional insight for designing efficacious vaccines and therapeutics against this deadly pathogen.
Keywords: B-1 cells; Bacillus anthracis; anthrax toxin; type 2 innate lymphoid cells.
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.