Spectrum of gut immunologic reactions: selective induction of distinct responses to Vibrio cholerae WO7 and its toxin

Past studies with Vibrio cholerae have shown that cholera toxin (CT) is mainly responsible for inducing T helper type 2 (Th2) responses with systemic IgG1, IgE and mucosal secretory IgA (sIgA) antibodies. In this study, V. cholerae WO7, which produces novel toxin unrelated to CT, was given orally to mice in order to determine whether the strain V. cholerae WO7 differs from V. cholerae 569B, which produces CT, in the nature of responses generated at the gut and splenic level. The analysis of immune responses evoked by V. cholerae WO7 in the gut of mice revealed striking differences as compared to those elicited by V. cholerae 569B infection. To assess the T helper cell type responses, lymphocytes from Peyer's patches and the spleen were stimulated in vitro for studying the cytokine patterns. PP and SP lymphoid cells from V. cholerae WO7 infected animals elaborated significant amounts of IL-2, IFN-gamma and IL-12 by 7 days p.i., suggesting a Th1 type of response. However by 15 days p.i., the PP and SP lymphoid cells secreted only IL-6 and IL-10 with traces of IFN-gamma. On the other hand, infection with V. cholerae 569B yielded mainly Th2 type responses at Peyer's patches as well as the splenic level. Infection with both V. cholerae WO7 and 569B induced toxin-specific IgA secreting cells at the gut and splenic level along with IgG1 secreting cells, indicating that both V. cholerae WO7 and 569B evoke an antigen-specific Th2 type of response in the gut as well as spleen. The persistence of IgA along with Th1-type cytokines indicates an alternate induction mechanism since mucosal IgA responses are usually associated with Th2-type responses. These observations are suggestive of a common mechanism employed by the host to clear different strains of V. cholerae infection (569B and WO7 in this case), while the nature of toxins elaborated failed to modulate the net outcome of the infection caused by V. cholerae.