Infection with Toxoplasma gondii Alters Lymphotoxin Expression Associated with Changes in Splenic Architecture

Abstract

ABSTRACTB cell responses are required for resistance toToxoplasma gondii; however, the events that lead to production of class-switched antibodies duringT. gondiiinfection have not been defined. Indeed, mice challenged with the parasite exhibited an expansion of T follicular helper cells and germinal center B cells in the spleen. Unexpectedly, this was not associated with germinal center formation and was instead accompanied by profound changes in splenic organization. This phenomenon was transient and was correlated with a decrease in expression of effector proteins that contribute to splenic organization, including lymphotoxins α and β. The importance of lymphotoxin was confirmed, as the use of a lymphotoxin β receptor agonist results in partial restoration of splenic structure. Splenectomized mice were used to test the splenic contribution to the antibody response duringT. gondiiinfection. Analysis of splenectomized mice revealed delayed kinetics in the production of parasite-specific antibody, but the mice did eventually develop normal levels of parasite-specific antibody. Together, these studies provide a better understanding of how infection withT. gondiiimpacts the customized structures required for the optimal humoral responses to the parasite and the role of lymphotoxin in these events.