The Systemic Immune State of Super-shedder Mice Is Characterized by a Unique Neutrophil-dependent Blunting of TH1 Responses

Host-to-host transmission of a pathogen ensures its successful propagation and maintenance within a host population. a striking feature of disease transmission is the heterogeneity in host infectiousness. it has been proposed that within a host population,20% of the infected hosts,termed super-shedders,are responsible for 80% of disease transmission. however,very little is known about the immune state of these super-shedders. in this study,we used the model organism salmonella enterica serovar typhimurium,an important cause of disease in humans and animal hosts,to study the immune state of super-shedders. compared to moderate shedders,super-shedder mice had an active inflammatory response in both the gastrointestinal tract and the spleen but a dampened th1 response specific to the secondary lymphoid organs. spleens from super-shedder mice had higher numbers of neutrophils,and a dampened t cell response,characterized by higher levels of regulatory t cells (tregs),fewer t-bet+ (th1) t cells as well as blunted cytokine responsiveness. administration of the cytokine granulocyte colony stimulating factor (g-csf) and subsequent neutrophilia was sufficient to induce the super-shedder immune phenotype in moderate-shedder mice. similar to super-shedders,these g-csf-treated moderate-shedders had a dampened th1 response with fewer t-bet+ t cells and a loss of cytokine responsiveness. additionally,g-csf treatment inhibited il-2-mediated th1 expansion. finally,depletion of neutrophils led to an increase in the number of t-bet+ th1 cells and restored their ability to respond to il-2. taken together,we demonstrate a novel role for neutrophils in blunting il-2-mediated proliferation of the th1 immune response in the spleens of mice that are colonized by high levels of s. typhimurium in the gastrointestinal tract. © 2013 gopinath et al.