Impaired Colonic B Cell Responses by Gastrointestinal Bacillus anthracis Infection

Anthrax is a zoonotic disease caused by the introduction of Bacillus anthracis endospores either by respiratory, oral, or cutaneous routes. With the gastrointestinal (GI) form of the disease, symptoms begin as nausea, vomiting, mild diarrhea, fever, and headaches, which soon progress into hemorrhagic diarrhea, hematemesis, ascites, and, eventually, septic shock and death. Virulent B. anthracis contains 2 plasmids (pXO1 and pXO2), for toxin production and capsule formation, respectively [1]. The pXO1 encodes protective antigen (PA), lethal factor (LF), and edema factor (EF); lethal factor cleaves mitogen-activated protein kinases (MAPKs) to subvert immune cells, while EF increases cellular levels of cyclic adenosine monophosphate (cAMP), causing edema [2]. PA binds to its receptors expressed on host cells and facilitates cellular entry of LF and EF. The nonphagocytic capsule that protects the bacteria from innate cells is encoded by pXO2 [3]. Both the respiratory and GI tracts are lined by mucosae; however, the presence of digestive enzymes and a greater microbial load differentiates these 2 locations. Commensal gut microbes and the immune system have coevolved over several million years [4]. One of the most common and effective responses of the mammalian host against bacteria is secretion of immunoglobulin A (IgA) at mucosal surfaces [5]. Gut mucosae secrete massive amounts of IgA, the lack of which causes dysbiosis [6]. Currently, B cells are grouped into 2 major classes, B-1 cells and B-2 cells. B-1 cells, which include CD5+ B-1a and CD5− B-1b subsets, differ from conventional B-2 cells in that they develop from fetal liver progenitors [7], represent the major B-cell subpopulation in the peritoneal and pleural cavities [8], and in steady state, produce germ line–encoded immunoglobulin M (IgM) and IgA to maintain commensals and resist common pathogens [9, 10]. B-1 cells are instrumental in producing antibodies without T-cell help, allowing for rapid antibody responses against microbial gut residents, including Bacillus species [11]. Several bacilli compose the gut microbiota [11]; therefore, IgA may play a critical role in controlling microbial infection, including GI B. anthracis infection. Hence, we hypothesized that B. anthracis interferes with B-1–cell function to establish active infection. Herein, we report that toxins secreted by B. anthracis impair immunoglobulin secretion and surface receptor expression on B-1 cells. Additionally, type 2 innate lymphoid cells (ILC2) that support the local expansion of B-1 cells [12] are compromised. These data strongly indicate that survival from infection necessitates neutralizing antibodies by expansion of germinal center B cells in the Peyer's patches and uncompromised function of B-1 cells and ILC2 in the gut.