Growth phase of orally administered Lactobacillus strains differentially affects IgG1/IgG2a ratio for soluble antigens: implications for vaccine development
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Abstract
Lactobacillus strains with probiotic activity are major constituents of numerous common
food products. Due to their 'generally regarded as safe'-status (GRAS-status), Lactobacillus
strains can also be genetically engineered for use in oral immunotherapeutic applications,
such as vaccination and T lymphocyte tolerance induction in autoimmune disease.In
the current study, we demonstrate that the growth phase of orally administered individual
Lactobacillus strains can differentially affect antigen-specific antibody subclasses
IgG1 and IgG2a, which might reflect skewing of systemic activity of T helper cell
type 2 (Th2) and T helper cell type 1 (Th1) pathways, respectively. Mice were orally
fed different wild type Lactobacillus strains in log phase or stationary phase and
immunized intraperitoneally with a T-cell dependent protein antigen. Sera were evaluated
for the ratio of antigen-specific IgG1 and IgG2a antibodies. Stationary Lactobacillus
murines and Lactobacillus casei cultures, but not two other Lactobacillus strains,
evoked significantly higher IgG1/IgG2a ratios than log phase cultures, possibly relating
to increased activity of the Th2-pathway. Despite normal variation in antibody responses
against TNP-CGG among individual mice, a high correlation was found between the IgG1
and IgG2a responses of mice within experimental groups. This differential antibody
response is likely due to growth phase-dependent differences in bacterial cell composition.Since
Lactobacillus growth phase dependent skewing of antibody responses possibly reflecting
T-cell pathways can inadvertently affect allergic and (auto)-immune responses, the
current findings strongly caution against unidimensional views on the oral administration
of individual Lactobacillus strains for probiotic or immunotherapeutic purposes, but
also suggest additional possibilities for immune modulation.