Eosinophils are required to suppress Th2 responses in Peyer's patches during intestinal infection by nematodes.

Infections with enteric nematodes result in systemic type 2 helper T (Th2) responses, expansion of immunoglobulin (Ig)G1 antibodies, and eosinophilia. Eosinophils have a supportive role in mucosal Th2 induction during airway hyperreactivity. Whether eosinophils affect the local T-cell and antibody response in the gut-associated lymphoid tissue during enteric infections is unknown. We infected eosinophil-deficient ΔdblGATA-1 mice with the Th2-inducing small intestinal nematode Heligmosomoides polygyrus and found that parasite fecundity was decreased in the absence of eosinophils. A lack of eosinophils resulted in significantly augmented expression of GATA-3 and IL-4 by CD4+ T cells during acute infection, a finding strictly limited to Peyer's patches (PP). The increase in IL-4-producing cells in ΔdblGATA-1 mice was particularly evident within the CXCR5+PD-1+ T-follicular helper cell population and was associated with a switch of germinal centre B cells to IgG1 production and elevated serum IgG1 levels. In contrast, infected wild-type mice had a modest IgG1 response in the PP, whereas successfully maintaining a population of IgA+ germinal center B cells. Our results suggest a novel role for eosinophils during intestinal infection whereby they restrict IL-4 responses by follicular T helper cells and IgG1 class switching in the PP to ensure maintenance of local IgA production.

Filariasis asymptomatically infected donors have lower levels of disialylated IgG compared to endemic normals.

Helminths induce strong regulatory and T helper 2-type responses, whereby antibody-derived host protection and regulation are essential components. Lymphatic filariasis is an immune-mediated spectral disease that manifests as two main clinical outcomes: chronic pathology or asymptomatic infection. These outcomes depend on a multitude of factors, including parasite-induced immunoregulation and host genetic background; antibody responses contribute to this outcome. N-glycosylation of the Fc region of antibodies is a post-translational modification required for the structure and molecular function, influencing host inflammatory and regulatory responses. Altered IgG glycosylation correlates with disease, whereby decreased galactosylation is associated with inflammation while increased sialylation is associated with anti-inflammatory responses. We purified N-linked glycans from the Fc region of total IgG from Wuchereria bancrofti-infected patients characterizing the two clinical manifestations (chronic pathology and asymptomatic infection) and compared them to infection-free endemic normals. Using capillary electrophoresis, we found that there was no difference in galactosylation of total IgG between the three groups; however, asymptomatically infected patients had significantly lower levels of disialylated IgG compared to endemic normals and patients with pathology. These data suggest that while galactosylation does not contribute to disease outcome, sialylation may be involved in asymptomatic infection.