Impaired colonic B-cell responses by gastrointestinal Bacillus anthracis infection.
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.
Department of Infectious Diseases and Pathology Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine.
Bikash
B
Sahay
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville.
Jennifer L
JL
Owen
Department of Infectious Diseases and Pathology Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine.
Mojgan
M
Zadeh
Department of Infectious Diseases and Pathology Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine.
Tao
T
Yang
Department of Infectious Diseases and Pathology Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine.
Yaíma L
YL
Lightfoot
Department of Infectious Diseases and Pathology Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine.
Firas
F
Abed
Department of Infectious Diseases and Pathology Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine.
Mansour
M
Mohamadzadeh
D000818:Animals; D000881:Anthrax / Q000276:immunology*; D001402:B-Lymphocytes / Q000502:physiology*; D001408:Bacillus anthracis / Q000276:immunology / Q000502:physiology*; D003106:Colon / Q000276:immunology / Q000382:microbiology; D005434:Flow Cytometry; D005767:Gastrointestinal Diseases / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction
B-1 cells; Bacillus anthracis; anthrax toxin; type 2 innate lymphoid cells